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U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

Public Health Service 

National Institutes of Health 



A 



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ti, 1 S. NATIONAL INSTITUTES OF HEALTH 
ANNUAL REPORT OF INTERNATIONAL ACTIVITIES 
FISCAL YEAR 1975 



Prepared by 
John E. Fogarty International Center 
for 
Advanced Study in the Health Sciences 



U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE 
Public Health Service 
National Institutes of Health 



DHEW Publication No. (NIH) 76-62 



For sale by the Superintendent of Documents, U.S. Government 
Printing Office, Washington, D.C. 20402 



ft is 



PREFACE 



This document is the seventh annual report of inter- 
national activities published by the John E. Fogarty Inter- 
national Center for Advanced Study in the Health Sciences. 
It contains a comprehensive narrative review and analysis 
of the international activities undertaken by the National 
Institutes of Health in FY 1975. Two companion booklets, 
NIH International Awards for Biomedical Research and 
Research Training/ FY 1975 and NIH Statistical Reference 
Book of International Activities, FY 197 5 , supplement this 
annual report. 

Within this review, the many international activities 
of the National Institutes of Health and their contribution 
toward broadening the knowledge base of the biomedical 
sciences dedicated to the improved health of American 
citizens as well as those of other nations are discussed. 
A significant part of NIH international activities, in- 
cluding the participation of distinguished foreign scien- 
tists in the Scholars-in-Residence program and Fogarty 
International Center conferences and symposia, as well 
as bilateral cooperation, was undertaken under the au- 
spices of the Fogarty International Center. Other acti- 
vities providing international biomedical cooperation 
have been conducted under the administrative purview of 
several institutes and divisions of NIH. These organiz- 
ations have contributed to the substantive content of this 
report with descriptive analyses of their activities, 
thereby providing a guide to the various types of NIH 
international programs. 

One important aspect of international cooperation 
that is very difficult to quantify, and one that has not 
been included in this document, is the informal exchange 
and sharing of information between professional colleagues 
in the United States and overseas. This cooperation, of 
course, is as valuable to the fulfillment of NIH mission 
as those other, more formal international cooperative 
activities described herein. 

This document was prepared by the International Coop- 
eration and Geographic Studies Branch, Fogarty International 
Center, Dr. Joseph R. Quinn , Chief. This branch is re- 
sponsible for the overall coordination within the Fogarty 
International Center of activities involving other govern- 
ments . 



Milo D. Leavitt, Jr., M.D. 

Director 

Fogarty International Center 



INTRODUCTION 



It has been the policy of the National Institutes of 
Health for many years to stimulate and support interna- 
tional biomedical research. Since the end of World War 
II, in particular, NIH also has sought to extend inter- 
national biomedical cooperation, recognizing, of course, 
that the exchange of data among scientists of many nations 
is fundamental to scientific progress. Thus, substantial 
research grant awards have contributed to the developing 
of productive working relationships between NIH and foreign 
laboratories. Other support of various kinds has also 
been instrumental in bringing foreign scientific competence 
to American science. Ultimately, these efforts seek to 
broaden the knowledge base of the biomedical sciences 
devoted to improved health for citizens of the United 
States and those of other nations. 

In pursuit of these research objectives NIH undertook 
numerous international activities during fiscal year 1975. 
In addition to the continuation of ongoing grant and train- 
ing awards, NIH scientists attended many international 
biomedical conferences, sponsored international symposia 
and seminars of various scientific and associated bio- 
medical problems, received distinguished foreign biomed- 
ical scientists, and published several books and papers 
advancing NIH research programs. The Fogarty International 
Center, as the point of coordination for the international 
activities of NIH, initiated or was involved in a sub- 
stantial part of the international cooperation in the 
biomedical sciences delineated in this report. 



CONTENTS 

Page 

Preface ...«.., iii 

Introduction i v 

I. Fogarty International Center: 

Concept and Programs i 

Conference and Seminar Program 5 

Scholars-in-Residence Program 10 

International Visitors Center 12 

International Research Exchange Program . . 13 

Visiting Program 15 

Special Foreign Currency Program 16 

International Education Program 21 

Gorgas Memorial Institute 28 

Bilateral Agreements for Cooperation in 

Biomedical Research 29 

Geographic Health Studies 35 

FIC as Coordinator for NIH International 

Activities 40 

II. International Cooperation in the Health 
Sciences by Components of NIH 

National Cancer Institute 45 

National Heart and Lung Institute 61 

National Institute of Allergy and Infectious 

Diseases 79 

National Institute of Arthritis, Metabolism, 

and Digestive Diseases 99 

National Institute of Child Health and 

Human Development 105 

National Institute of Environmental Health 

Sciences Ill 



Page 

National Library of Medicine 121 

NIH Assistance to WHO and PAHO 129 

United States Fellows and Trainees 

Abroad 131 

Guest Workers 131 



I 

FOGARTY INTERNATIONAL CENTER 
CONCEPT AND PROGRAMS 



FOGARTY INTERNATIONAL CENTER: 
CONCEPT AND PROGRAMS 



In a speech before the Third National Conference on 
World Health in September 1963, Representative John E. 
Fogarty introduced the concept of a center to represent 
"...the visible and tangible embodiment of the nation's 
devotion to the use of science for peaceful purposes and 
the good of mankind." He envisaged a study center that 
would "... encompass conference facilities, laboratory and 
study space, and the living quarters to permit the assembly 
for discussion, study, and research of the outstanding 
health scientists of the world." Representative Fogarty 
died on January 10, 1967, before the realization of this 
concept. After his death, however, then Congressman 
Melvin Laird proposed the establishment of such a center 
as a living memorial to Mr. Fogarty. The Congress and 
the President approved this proposal, and on July 1, 1968, 
the John E. Fogarty Center for Advanced Study in the 
Health Sciences was realized. 

The close of FY 1975 records the completion of the 
seventh year of operations for the Fogarty International 
Center. During the course of these years several programs 
have emerged as the principal activities of the Center and 
from which the Center has derived much of its character 
in attempting to fulfill the concept of Representative 
Fogarty and the Honorable Melvin Laird. 

Generally, the Center's programs were designed to pro- 
mote advanced study in the biomedical and related sciences 
and to develop practical methods to utilize the knowledge 
thus, gained to improve the health and well-being of our 
contemporary society. The Center's programs encourage 
interaction, study, cooperation, and collaboration within 
the international biomedical community and provide oppor- 
tunities for study and discussion of significant research, 
public health, medical, and biomedically related social 
and economic issues. 

Specifically, the projects that constitute the general 
programs delineated above and that have developed within 
the Center over the past 7 years constitute a substantial 
spectrum of research and administrative support activities. 
One such program involves studies on preventive medicine 
that ultimately seek to investigate 15 areas of preventive 
medicine, including diseases of fetal development, trauma, 
emergencies and emergency care, communicable diseases, 
gastropathy, and endocrine and metabolic diseases. Another 
highly relevant and successful project involves the compi- 
lation and analyses of biomedicine and health care in a 
number of selected countries, with special emphasis upon 
the Soviet Union and the People's Republic of China. 



Several studies covering various aspects of biomedicine 
and health care in the Soviet Union and China have been 
published over the past 7 years and several others are 
planned or in progress. 

Still another imaginative project undertaken by the 
Center is the Scholars-in-Residence program whereby dis- 
tinguished scholars undertake a period of residence at 
the Center to engage in research, individual study, and 
group interaction designed to produce original contribu- 
tions toward advancing biomedical knowledge and to facili- 
tate the exchange of ideas among biomedical scholars. 
Also of considerable current and potential significance 
is the bilateral cooperation in biomedical research with 
19 foreign countries in which the Center serves to coor- 
dinate efforts for the United States Government. Although 
this cooperation is governed in most instances by agree- 
ments between the United States and other governments, 
there have been times when this cooperation has been 
attained through more informal bilateral arrangements. 
Thus far, this cooperation has yielded knowledge of foreign 
biomedical research and health care, as well as direct 
contributions to the advancement of American biomedical 
knowledge by foreign scientists. 

In addition to these programs and projects briefly 
described above, the Center has engaged in several admin- 
istrative programs designed to advance biomedical and 
related scientific knowledge in the United States: 

1. Special Foreign Currency program (Public Law 480), 
which enables NIH to support biomedical research in 
"excess currency" countries abroad; 

2. International Visitors Center, which serves as a 
focal point for the reception of foreign scientists; 

3. International Research Exchange program, which 
has provided numerous opportunities for highly qualified 
foreign biomedical scientists to engage in advanced 
research in leading research institutions in the United 
States; and 

4. International Education program, under which 
arrangements are made in the United States for biomedical 
training for foreign nationals receiving WHO and UN fellow- 
ships in the health sciences. 

Finally, during our short past, the Center has provided 
a general coordinating function for all NIH international 
activities. In this role, the Center has reviewed foreign 
grants and contracts, published biomedical data from 
scientific observers abroad, and disseminated information 
to NIH obtained from participants in international scientific 



conferences and symposia. 

In summary, then, the Fogarty International Center 
for Advanced Study in the Health Sciences is attempting: 

1. To promote advanced study in the health sciences 
through various mechanisms, such as conferences and 
seminars, support of scholars in residence on NIH campus, 
publications, and bilateral and multilateral cooperation; 

2. To identify the legal, ethical, social , and eco- 
nomic problems that may arise from continuing biomedical 
research and to advance our understanding and insight into 
these problems; and 

3. To stimulate research concepts in specific fields 
through interaction among the international and domestic 
biomedical research community. 

There follows a description, in some detail, of the 
previously referenced FIC program and project operations 
during FY 1975 through which the Fogarty International 
Center staff sought to fulfill the several objectives set 
forth above. 



Conference and Seminar Program 

As part of the advanced study concept, the Conference 
and Seminar program sponsors interaction and collaboration 
among members of the international biomedical community 
and provides opportunities for study and discussion of 
significant biomedical, public health, and related social 
and economic issues. 

In practice, the Conference program is developed 
around current directions in medical, biological, and be- 
havioral sciences. Many of the meetings are in direct 
support of the research activities of the NIH, and criteria 
for sponsoring of conferences include a broad interest 
within the scientific objectives in addition to information 
exchange, and international priority. 

Conferences convened to date can be classified into 
several conceptual areas: preventive medicine and health 
care delivery, environmental health, medical education, 
international health research and education, ethical and 
social problems in biomedicine, and advanced topics in 
biomedical research. 



Preventive Medicine 

and 
Health Care Delivery 



Improvement in the health status of the American 
people depends in great measure on the design and applica- 
tion of programs that emphasize the preventive aspects of 
human disease problems. Although health authorities 
generally agree with this thesis, a more precise defini- 
tion is needed of effective methods or programs of preven- 
tion, financial resources required to implement these 
programs, and priorities to be assigned to research in 
preventive methodology. The need to assemble expertise 
in this field to elucidate mechanisms whereby the full 
impact of preventive medicine can be brought to bear on 
the solving of America's major health problems has been 
emphasized by the Office of the Assistant Secretary, DHEW, 
in the Forward Plan for Health. 

Three years ago the Fogarty International Center ini- 
tiated a series of comprehensive studies in preventive 
medicine. These studies, oriented by disease category, 
are charged to review and evaluate the state of knowledge 
and research in the prevention and control of human disease; 
identify knowledge gaps and areas requiring further research, 
including analysis of financial resources, techniques, 
and manpower; and identify problems encountered in apply- 
ing preventive medicine and suggest corrective actions. 

The first planning session of the organizational com- 
mittee identified 15 major disease categories for detailed 
review by individual subcommittees. Of the six subjects 
selected for initial consideration, studies of diseases of 
fetal development and the neonatal period, derangements 
of dental health, communicable diseases, diabetes, and 
obesity have been completed and published. Additional 
subcommittees have been activated to consider renal disease, 
nutritional derangements, arthritis, maternal and child 
health, trauma, screening and health maintenance, and 
economic impact of ill health. 

In an effort to coordinate divergent activities in 
preventive medicine, the Fogarty International Center has 
also undertaken a cooperative program with the Association 
of Teachers of Preventive Medicine. Designed to develop 
resource material for departments of preventive medicine, 
this program has the following objectives: to create 
resource material for individual departments in adminis- 
tration, teaching, research, and service; define depart- 
ment goals and enhance collaborative activity among depart- 
ments of preventive medicine and other departments of 
health science schools; promote cooperative activities 



among departments of preventive medicine via national 
joint teaching, research, and service programs; and pro- 
vide consultative services to other agencies. The Fogarty 
Center has also cooperated with the Milbank Memorial Fund 
in its study of higher education for public health. 

Among the 10 subjects considered, all have been 
completed and published: 

-- New Health Practitioners 

— Teaching of Chronic Illness and Aging 

— Chronic Childhood Illness - Assessment of Outcome 

— Behavioral Sciences 

— Preventive and Community Medicine in Primary Care 
-- Consumer Participation in Health Care 

— Toward an Educated Health Consumer 

— International and Extramural Teaching and Research 
Resources in Preventive Medicine 

— Academic Relationships Between Preventive Medicine 
and Public Health 

— National Teaching Resources in Preventive Medicine 

To further assist coordination of preventive medicine 
in the United States, the Fogarty Center sponsored a 
National Conference on Preventive Medicine in June 1975, 
in which over 200 specialists in preventive medicine and 
allied fields participated. During the preceding year, 
eight Task Forces developed position papers in the areas 
of: historical perspective of preventive medicine in the 
U.S.; theory and practice of prevention in environmental 
health, delivery of preventive care in personal health 
services, social determinants of human health, consumer 
health education, training of health professionals for 
prevention, economic impact of preventive medicine, and 
quality control and evaluation. These task force reports 
were reviewed by the conference participants and recom- 
mendations were made for their implementation and for 
subsequent planning. The conclusions of the Task Forces 
were incorporated into DHEW Forward Plan for Health 
1976-80. 

Environmental Health 

Conferences on environmental health topics have been 
sponsored in collaboration with the National Institute of 
Environmental Health Sciences. These meetings were in 
response to increased awareness of the contribution of 
the environment to disease processes and in support of 
the U.S. delegation to the UN conference, "Man and the 
Environment." The topics-controversy regarding the precise 
effect of environmental pollutants, uncertainty about the 
mechanisms by which they produce their effects, or simply 
lack of information as to the extent of the problem- 



explored the roles of metallic contaminants, mutagenic 
agents, and multiple environmental factors in producing 
disease and the contribution of environmental factors to 
respiratory disease. These workshops have been made 
available to the public by publication. 

Medical Education 

This conference series developed largely in response 
to student unrest in the 1960's. This unrest reflected 
the need to revise medical curricula, making education 
more responsive to community needs. As a result, depart- 
ments of community or social medicine were established and 
family practice came to be recognized as a speciality. 
The conferences sponsored by the Fogarty Center considered 
the student pressure for curriculum reform internationally, 
the role of biomedical research in the education of 
physicians, and the relationships between health care and 
medical education in the medical school. These conferences 
have all been published. 

International Health 
Research and Education 

Biomedical research and medical education are inex- 
tricably linked and mutually dependent on one another for 
their continued advancement and vitality. Institutions 
of medical education serve several purposes, tradition- 
ally represented by the triad of education, research, 
and service. In addition to training those who will pro- 
vide health care, medical schools strive to cultivate an 
atmosphere conducive to research and to train those who 
will pursue careers in research and teaching. 

Central to the purposes is the belief that virtually 
all countries share common problems and goals in educating 
and training health care providers. Direction and leader- 
ship are necessary in order to achieve the highest possible 
standards of medical care. Differences in approach to that 
goal are more a reflection of differences of cultural, 
social, and economic characteristics than of purpose. It 
is reasonable to believe that sharing ideas and experiences 
can be mutually beneficial. 

The general objectives of the program follow: 

— To serve as a focal point within the Fogarty 
International Center and the National Institutes of Health 
for matters relating to international medical education 

at both undergraduate and postgraduate levels; 

— To accumulate, classify, and maintain information 
about current and changing patterns of medical education 
in advanced and developing, countries; 



— To evaluate such information with respect to health 
care problems and needs of individual countries and with^ 
in the framework of their socioeconomic, cultural, and 
political characteristics; 

— To compare systems of medical education with one 
another and with established or changed patterns of 
medical education in the United States; 

— To initiate, support or assist the development 
of individual or collaborative studies or programs 
pertinent to its mission. 



Ethical and Social Problems 
in 
Biomedicine 

The Center has sponsored conferences on various social 
and ethical problems arising from advances in biomedical 
research and the application of these advances to medical 
care. The Center is ideally suited to this role, since it 
represents a nonpartisan meeting ground for discussion of 
these controversial areas. Topics considered have included 
changing family structure and control of human repro- 
duction; new technological abilities for early diagnosis 
of human genetic disease and detection of persons who 
may transmit genetic disease to their offspring; the 
prospects for treatment of patients with genetic disease, 
and the ethical issues involved in genetic counseling; 
and the health hazards involved in experimentation with 
oncogenic and infectious viruses. 



Advanced Topics in Biomedical Research 

Support of meetings in this category is in 
recognition of the important role of research in the 
understanding of disease processes and in the development 
of early detection and better treatment of illness. Many 
of these conferences have provided support for the research 
activities of the various NIH institutes. 

In addition, Fogarty Scholars and U.S. and foreign 
academicians have participated in identifying key problems 
in basic and clinical research that should be explored 
by bringing together scientists in various fields. 
Conferences sponsored recently include; 

-<- Cell Surfaces and Malignancy 

— Chemistry and Biology of the Kallikrein-Kinen 
System 



10 



— Modification of Host Immune Resistance in the 
Prevention and Treatment of Neoplasia 

— Structure and Function of Fluorescing Cells 

— Chemistry, Biology, and Political Aspects of Uses 
of the Atmosphere 



Scholars-in-Residence Program 

Crucial to the study center concept, this program 
facilitates the work of individual scholars and the ex- 
change of ideas among scholars, distinguished science 
leaders, science administrators, and promising young 
scientists. Individuals accepting an invitation to par- 
ticipate in the program are known as "Fogarty Scholars" 
during their period in residence. Invitations are limited 
to persons of distinction who - in the judgment of the 
director of the Center, his staff, and advisors - have the 
educational and cultural background plus research exper- 
ience to make significant contributions to advanced study 
in national boundaries. 

Scholars and invited participants are not limited 
solely to experience in the biomedical disciplines; they 
may also consider studying philosophic, social, economic, 
or legal issues related to health science. While in resi- 
dence each scholar participates in one or more of the 
following types of activity: 

1. Individual study : The scholar may make an assess- 
ment of the state of the art or a prospective study in a 
specific field. This approach can be directed toward 
preparation of a book, monograph, or scientific report. 
Working primarily on an individual basis, the scholar is 
encouraged to participate in other NIH workshops, confer- 
ences, and seminars. 

2. Group Interaction : The scholar might prefer to 
collaborate with other scholars and invited consultants in 
considering a common topic for the purpose of developing 
recommendations or suggestions for the advancement of 
biomedical knowledge. 

3. Research : At the invitation of an institute, the 
scholar might choose to spend a portion of his time in the 
laboratory. As a Fogarty Scholar, however, he is encouraged 
to participate in FIC-sponsored workshops, conferences, and 
seminars when appropriate . 

The sum of $210,867 was expended from Fogarty Inter- 
national Center FY 1975 funds for the Scholars-in-Residence 
program. The following 14 distinguished scientists were 



11 



Scholars-in-Residence during FY 1975: 

Dr. Karl Beyer, Visiting Professor, Department of 
Pharmacology, Milton S. Hershey Medical Center, Penn- 
sylvania State University, Hershey, Pennsylvania. 

Dr. Daniel Bovet, Professor of Psychobiology , Uni- 
versity of Rome, Rome, Italy. 

Dr. Ronald V. Christie, Professor Emeritus, Office 
of the Dean, McGill University, Montreal, Quebec, Canada. 

Dr. Hugh Davson, Honorary Research Fellow, Depart- 
ment of Physiology, University College London, London, 
England. 

Dr. Olavi Eranko, Professor and Chairman, Department 
of Anatomy, University of Helsinki, Helsinki, Finland. 

Dr. George E. Godber, (Former) Chief Medical Officer, 
Department of Health and Social Security, United Kingdom, 
London, England. 

Dr. Ragnar Granit, Professor Emeritus, Nobel Insti- 
tute for Physiology, Karolinska Institutet, Stockholm, 
Sweden . 

Dr. Gordon G. Hammes, Professor and Chairman, Depart- 
ment of Chemistry, Cornell University, Ithaca, New York. 

Dr. Abraham Horwitz, Director Emeritus, Pan American 
Sanitary Bureau, Washington, D.C. 

Dr. Elvin A. Kabat, Professor, Department of Micro- 
biology, College of Physicians and Surgeons, Columbia 
University, New York, New York. 

Dr. Herman M. Kalckar, Visiting Professor, Biological 
Chemistry, Harvard University Medical School, Boston, 
Massachusetts . 

Dr. Charles P. Leblond, Professor and Chairman, 
Department of Anatomy, McGill University, Montreal, Quebec, 
Canada. 

Dr. Dirk W. Van Bekkum, Director, Radiobiological 
Institute, Institute for the Organization for Health 
Research, Rijwijk, The Netherlands. 

Dr. Paul C. Zamecnik, Director, Colis P. Huntington 
Labs, Massachusetts General Hospital, Boston, Massachusetts 



12 



International Visitors Center 

This major program service of the Fogarty Interna- 
tional Center receives scientists from all parts of the 
world. The Visitors Center is responsible for developing 
appointments for foreign scientists and dignitaries at 
NIH and coordinating them with their visits to other 
research centers. 

During FY 1975, 195 of the 247 visitors were from 43 
foreign countries and represented every part of the 
academic world. The U.S.S.R. sent 24, the largest number 
of visitors; followed by the People's Republic of China 
with 19, France with 17, the Federal Republic of Germany 
with 14, and Italy with 13. Among the distinguished 
visitors to NIH were Mr. Osman Dana, Minister of Health 
of Lebanon; Prof. Hubert Curien, Director, General Dele- 
gation for Scientific and Technical Research (DGRST) , 
France; Dr. Philippe Laudat, Scientific Director of INSERM, 
France; Dr. A. P. Burger, Vice President of CSIR, Union of 
South Africa; and Mr. Emile Krieps , Minister of Health of 
Luxembourg. Principal areas of interest to the visitors 
were laboratory science, 54 visitors; administrators, 51; 
medical science, 20; and medical educators, 18. 

In November 1974, an eight-member pharmacology dele- 
gation from the People's Republic of China visited NIH, 
followed in May 1975 by the visit of an eleven-member 
molecular biology delegation. Both delegations were spon- 
sored by the National Academy of Sciences. 

Another responsibility of the Visitors Center is 
administrative management of the NIH Visiting Program, in 
which international scientists participated during FY 1975. 
Services included assistance with housing and other living 
arrangements in the area, health insurance, income taxes, 
visas, local educational facilities for dependents, pre- 
paration and processing of appointment documents and ed- 
ucational counseling for participants and other scientists 
who are seeking career opportunities away from NIH. Analy- 
sis of the program follows under a separate heading. 

The Visitors Center also assisted 184 guest workers 
from 42 nations at NIH during FY 1975 with many of the 
same services rendered to scientists in the Visiting Program. 



13 



International Research Exchange Program 



In Section 307 of the Health Services Research, 
Health Statistics, and Medical Libraries Act of 1974, 
Congress authorized the Public Health Service to parti- 
cipate with other countries in cooperative endeavors in 
biomedical research to "establish and maintain fellow- 
ships in the United States and in participating foreign 
countries." Under this legislation the Fogarty Inter- 
national Center offers International Research Fellow- 
ships and Senior International Fellowships. These fellow- 
ships are offered in conjunction with the International 
Research Exchange program, which evolved from an extension 
to citizens of other countries (on September 16, 1957) of 
the regular NIH Postdoctoral Research Fellowship program. 
These fellowships were administered by the Division of 
Research Grants until the international portion was trans- 
ferred to the Office of International Research at NIH in 
1961. In 1968 the newly established Fogarty International 
Center assumed the administration of the International 
Research Fellowship Program. 

One thousand five hundred twenty-four new fellowships, 
funded under the program from FY 1958 through FY 1975, 
have provided opportunities for carefully selected highly 
qualified foreign biomedical scientists to participate 
in research under the tutelage of leading American scien- 
tists. Each year applications from prospective fellows 
are reviewed competitively for scientific merit by a panel 
of experts convened at NIH. Applications are assigned 
priority scores by the reviewers, fellowships awarded 
according to this ranking, and the amount of funds appro- 
priated for the program for that year. 

International fellows have made significant contri- 
butions to the research programs of their preceptors in 
their host laboratories, thereby advancing the United 
States capability for diagnosis, treatment, or prevention 
of disease. The fellows bring different points of view 
to research problems and sometimes introduce new and in- 
novative methodology developed abroad. Typically, they 
exhibit a high capacity for hard work and diligent devotion 
to research as reflected in their active participation in 
seminars and discussions and through their numerous pub- 
lications in scientific literature. In FY 1975, 76 new 
International Research Fellowships and 26 second-year 
fellowships were awarded, at a total cost of $1,344,306. 

In August 1974, with the establishment of the Senior 
International Fellowship program, the program of NIH-spon- 
sored fellowships became a two-way exchange. The senior 
program enables carefully selected midcareer American 



14 



academic faculty members to work in the place of their 
choice abroad. The purpose of the program is to increase 
the interchange of ideas of mutual interest in basic or 
clinical research and academic studies. It is intended 
that the award will be a career-enhancing experience with 
mutual benefit to the fellow and his foreign host. Awards 
are made on the basis of scientific merit of the appli- 
cation and the competition is keen. During FY 1975, 28 
Senior International Fellowships were selected for award 
from 45 applications. The funds expended for this pro- 
gram amounted to $444,227. 

Another portion of the International Research Exchange 
program administered by the Fogarty International Center 
is the group of fellowships offered to young American 
postdoctoral scientists by the Swedish Medical Research 
Council and the Swiss National Science Foundation. Each 
year these two countries sponsor three fellowships each. 
The Fogarty International Center advertises this - program 
annually, sends out application kits, and reviews appli- 
cations for the two sponsoring countries. The review 
procedure is the same as for the International Research 
Fellowships; the applications with their assigned priority 
scores are forwarded to Sweden or Switzerland for final 
selection of the fellows by the sponsor. Since 1964 the 
Swedish Government has sponsored 28 American fellows; the 
Swiss have sponsored 9 since their program was established 
in 1973. 



15 



Visiting Program 

Initiated in August 1950, this program sought the 
participation and assistance of outstanding young scien- 
tists for specialized research training as Visiting 
Fellows and for substantive contributions to the progress 
of NIH research as Visiting Associates and Visiting Scien- 
tists. Many centers of scientific research in the United 
States and abroad will benefit from the training and ex- 
pertise acquired by these scientists in the NIH Visiting 
Program. 

The growth pattern of the program has continued at a 
constantly accelerating rate. In FY 1965 there were 157 
participants at a cost of $1.2 million; in FY 1970, 214 
at $2.1 million; and FY 1974, 433 at $4.8 million. The 
following table contrasts the two most recent years: 

FY 1975 

Visiting Fellows 302 

Visiting Associates 121 
Visiting Scientists 121 

Total participants 544 
Total countries 51 

Total cost $6.5 mil. 

In FY 1975, the following countries sent the most 
scientists in the Visiting Program: Japan 117, India 64, 
United Kingdom 43, Israel 38, Italy 31, and Taiwan 28. 
In addition, NCI had the largest number of Visiting Pro- 
gram participants with 133, followed by NIAMDD with 86. 

Under this program, NIH bureaus, institutes, and 
divisions invite scientists of their choice to participate 
in one of the three program categories. In contrast to 
Visiting Associates and Scientists, whose award is for the 
performance of services for NIH, the Visiting Fellows' award 
supports postdoctoral research training. Awards are made 
to individuals with a doctoral degree in a health science 
field whose postdoctoral experience does not exceed 3 
years. The sponsor of the Visiting Fellow is expected to 
provide educational opportunities similar to those pro- 
vided by university faculty members to their postdoctoral 
fellows . 



FY 1974 




231 




106 




96 




433 




47 




$4.8 mi 


1 



16 



Special Foreign Currency Program 



The National Institutes of Health (NIH) Special 
Foreign Currency Program, imprecisely referred to as 
the "PL 480 program," enables NIH to participate in 
collaborative research efforts of the international 
biomedical research community and to utilize resources 
of selected countries to further the attainment of the 
domestic goals of the institutes and of the host 
countries. This program brings the talents of U.S. 
scientists and those from other countries to bear on 
biomedical science and information exchange problems of 
mutual interest. It is funded with currencies, designated 
by the Department of the Treasury as excess to the immediate 
needs of the U.S. that have primarily accrued under Public 
Law 480 from the sale in past years of surplus agricultur- 
al products. Thus, it neither contributes to the flow 
of dollars abroad nor uses new tax revenues. 

The collaborative character of the NIH program 
requires that there be a scientist from NIH (intramural) 
or a U.S. academic institution (extramural) as a partici- 
pant. Research projects are selected by individual insti- 
tutes on the basis of technical merit and potential 
contribution to institute research objectives. Projects 
are also subject to review within the host country for 
technical merit and conformance with its national 
priorities. The research activities are conducted under 
formal agreements entered into by NIH, as an agency of the 
United States, and the foreign government. 

Funds for the Special Foreign Currency program are 
derived from the appropriation for "Scientific Activities 
Overseas," which for presentation purposes appeared in 
the NIH appropriation for several years and was trans- 
ferred to the Office of the Assistant Secretary for Health 
(ASH) in FY 1975. The Office of International Health 
of ASH/DHEW has responsibility for formulating policy 
for administering the appropriation for the Special 
Foreign Currency program. Funds are allotted to NIH on 
the basis of conformance of projects to programs and 
priorities of DHEW and priorities of foreign countries 
negotiated by DHEW. The excess currency countries during 
this fiscal year were Burma, Egypt, Guinea, India, Paki- 
stan, Poland, and Tunisia. 

The U.S. -owned currencies in Israel and Yugoslavia 
have been reduced so that they are no longer "excess," 
and funds are no longer available in these countries for 
new projects or continuation of previously supported 
projects. This has severely curtailed the collaboration 
with the biomedical science communities afforded by this 



17 



program. In an effort to attenuate the severity of the 
financial impact and disruption of research programs 
and to formally recognize the need for maintaining 
collaboration, the Department of State has negotiated 
bilateral agreements with the governments of Israel and 
Yugoslavia through which remaining funds have been made 
available during a phaseout period to provide time 
in which to obtain replacement support. To avoid the 
disruption of the scientific community experienced in 
Israel and Yugoslavia, in the event of depletion of the 
U.S. balance of Polish currency, the long-standing agree- 
ment for health science cooperation with Poland has been 
amended recently. During this fiscal year bilateral 
agreements, which include a biomedical research component, 
haye also been negotiated with Egypt and India. These 
bilateral agreements establish policies, procedures, and 
priority- areas of mutual interest to which the NIH 
Special Foreign Currency program must conform. They 
will have a significant impact upon the development 
of the NIH SFC program and will become a major influence 
on its character. A more detailed review of the five 
agreements follows. 

Israel 

In FY 1968 it became apparent that balances of U.S.- 
owned Israeli pounds were depleted to the point where funds 
would no longer be available. The full impact of this 
depletion was realized by NIH in FY 1973, when the first 
projects reached the end of their previously committed 
period of support and could not be continued. 

In anticipation of this, the Department of State 
and the Israeli government signed an agreement on 
September 27, 1973, establishing the U.S. -Israel Binational 
Science Foundation, to which each country contributed 
equal amounts of Israeli pounds in a total equivalent to 
$6 million. The income from the investment of these 
funds provides for some new activities as well as the 
continuation of projects and collaborations previously 
established under the Special Foreign Currency program. 
Approximately $2.1 million (equivalent) is available 
annually from this source to all U..S. Government agencies 
for the support of scientific and technological collabora- 
tion. 

Either U.S. or Israeli scientists may apply for 
support, provided their requests represent collaborative 
research efforts. Applications are submitted to the 
Executive Director of the foundation in Jerusalem. The 
foundation arranges for technical merit evaluation of all 
applications, sending them to both U.S. and Israeli 
scientists by mail. From the projects that have passed 
this review, the Board of Governors of the foundation makes 
the final selection for funding. The foundation operates 



18 

independently of NIH, with the exception that NIH is 
requested to review projects to be funded for relevance 
to NIH biomedical research programs. 

Yugoslavia 

In March 1972 an accounting revealed that the U.S.- 
owned dinar holdings in Yugoslavia had been obligated 
by the science and technology agencies to such an extent 
that the currencies would no longer be in excess and that 
a maximum of $7.2 million (equivalent) was available 
for FY 1973 and FY 1974. 

The Department of State negotiated the "agreement 
between the Government of the United States of America 
and the Government of the Socialist Federal Republic of 
Yugoslavia on scientific and technological cooperation," 
which was signed on May 18, 1973, by the Director, Bureau 
of International Scientific and Technological Affairs, 
Department of State, on behalf of the United States, and 
Mr. Krsto Bulajic, Director General, Federal Administration 
for International Scientific, Education, Cultural, and 
Technical Cooperation, on behalf of Yugoslavia. This 
agreement established a joint fund for the support of 
scientific and technological projects, including health, 
and a U.S. -Yugoslav joint board on scientific and techno- 
logical cooperation to administer the fund in the amount 
of $14.4 million (equivalent) from equal dinar contribu- 
tions by each country. At a meeting of the joint board 
May 14-18, 1973, it was apparent that the income from 
this fund would have little effect in moderating loss 
of financial support; the decision was then made to commit 
all the funds to provide limited support for projects 
during a phaseout period of 3 years. NIH was allotted 
funds for 24 projects. All active NIH projects in 
Yugoslavia are now operating with financial support from 
the joint fund. 

The U.S. -Yugoslavia bilateral agreement has a unique 
provision for matching U.S. dollar support of any former 
NIH/SFCP or new research project of mutual interest on an 
equal-share matching basis through the joint fund admini- 
stered by the U.S. -Yugoslavia joint board on scientific 
and technological cooperation. 

Poland 

A memorandum of understanding between the United 
States and Poland, signed March 14, 1962, designated 
NIH as the focus for development of a collaborative 
research program in the biomedical sciences. NIH served 
in this role until FY 1965 when in an effort to expand 
the scope of the program by involving other DHEW 
agencies, responsibility for administration and program 
development was transferred to the Office of International 



19 

Health, at that time in the Office of the Surgeon General 
of the Public Health Service and now in the Office of 
the Assistant Secretary for Health. 

On March 15, 1973, during the visit of the Minister 
of Health of Poland, a revised memorandum of understanding 
was signed by the Secretary of DHEW and Dr. Marian 
Sliwinski, the Polish Minister of Health. For the 
first time this agreement formally provided for the 
exchange of scientists and the development of mutually 
agreed-upon priorities and the annual review and revision 
of these priorities. 

On October 8, 1974, during the visit of Mr. Edward 
Gierek, First Secretary of the Polish United Workers 
Party, the health agreement of 1973 was revised and 
raised to the status of a "country- to-country" agreement 
and signed by the Secretary of State and Mr. Mieczyslaw 
Jagielski, Deputy Prime Minister and Chairman of the 
Planning Commission of Poland. This agreement included 
two new provisions: establishment of a U.S. -Polish 
joint committee for health cooperation and funding of 
DHEW projects for the Marie-Sklodowska Curie Fund. This 
joint fund was established by the agreement "Funding of 
Cooperation in Science and Technology," which was also 
signed at that time by the Secretary of State and 
Minister Jagielski. This document, which also provided 
for the establishment of a U.S. -Polish joint board, was 
an implementation of the "science and technology coopera- 
tion agreement" signed in October 1972 during the visit 
to Poland of the President of the United States. 

With the establishment of the joint board and the 
joint fund, the Polish government has agreed to match the 
sums that DHEW deposits for support of NIH and other 
DHEW agency research projects. The administrative pro- 
cedures incidental to operation of the fund are under 
development. The joint board selected nine NIH projects 
in the amount of $1,113,000 (equivalent) for support from 
the joint fund. These concern the neurosciences and 
immunologic and metabolic processes. 

The priorities were given a second annual review at 
a meeting of the joint board on U.S. -Polish medical coopera- 
tion; it was agreed that those in effect during the past 
year would be continued. It was also agreed that oncology, 
which had been removed from the original list at the time 
of the first annual review because of lack of activity, 
would be reinstated as the result of recent developments 
in this field. The current priorities are (1) occupational 
and environmental health, (2) rehabilitation, (3) neurologic 
and psychiatric diseases, (4) health problems related to 
food and drugs, (5) infectious diseases and the immune 
system, (6) planning, delivery, and evaluation of health 
services, especially those to mothers and children, and 



20 

(7) oncology, 

Egypt 

An agreement on "principles of relations and coopera- 
tion between Egypt and the United States" was signed by 
Muhammed Anwar el-Sadat, President of the Arab Republic 
of Egypt, and by the President of the United States on 
June 14, 1974. The agreement established joint working 
groups for Suez Canal reconstruction, trade and economic 
growth, agriculture, technology, research and development 
in science, and medical cooperation. The purpose of 
the medical cooperation group, as stated in the agreement, 
is "... to assist the Government of Egypt to develop 
and strengthen its medical research, treatment, and 
training facilities." The joint working group on medical 
cooperation held its first meeting in Cairo October 28- 
November 1, 1974, at which time priority areas for coopera- 
tion were identified: (1) strengthening of health services, 
(2) health manpower and medical education, (3) production 
of pharmaceutical, biological, and medicinal products, 
(4) environmental health, and (5) biomedical research. 
During this meeting the delegates also prepared a prelimina- 
ry delineation of the scope of each of the above priorities 
for consideration and development in greater detail by 
subsequent panels of expert consultants. 

At the second meeting of the joint working group, 
July 7-11, 1975, it was found that other subcommittees 
for the aforementioned areas had subsequently assumed 
responsibility for some aspects of the biomedical sciences. 
The decision was made to appoint U.S. and Egyptian 
representatives to give further consideration to the needs 
of biomedical research in Egypt and, as appropriate, to 
identify priorities to replace those developed previously. 

India 

An "agreement between the Government of the United 
States of America and the Government of the Republic 
of India to establish a joint commission on economic, 
commercial, scientific, technological, educational, and 
cultural cooperation" was signed on October 28, 1974, 
by Secretary of State Kissinger and Mr. Y. B. Chavan, 
Minister for External Affairs of the Republic of India. 
The agreement provided for establishing subcommissions for 
the fields of economic and commercial development, 
scientific and technological cooperation, and education 
and cultural cooperation. Health was included, with 
industry and agriculture, as a responsibility of the 
subcommission on science and technology. The first 
meeting of this subcommission was held in Washington, 
D.C., January 27-29, 1975, during which priority areas 
were agreed upon as the basis for the program of coopera- 
tion. During the development of these priorities by the 



21 



subcommission, a major objective of the Indian delegation, 
comprised of representatives of the Ministry of Health 
and the Indian Council of Medical Research, was to assure 
that collaborative research efforts be directed toward 
investigations of those aspects of problems of importance 
to India. A further objective was the identification of 
new or additional researchers and institutions with the 
capability of carrying on productive research programs. 
The priority areas agreed upon for collaboration in the 
biomedical and health sciences are (1) communicable and 
infectious diseases, with particular emphasis on prevention 
and control techniques for such diseases as tuberculosis, 
leprosy, malaria, filariasis, (2) reproductive biology 
and fertility control, (3) health delivery systems for 
efficient utilization of medical and paramedical manpower, 

(4) nutritional, metabolic, and degenerative diseases, 

(5) toxicologic research in naturally occurring toxins 
in foods, pesticides, and drug residues, (6) other such 
areas of biomedical and health science research as may be 
proposed and agreed upon as being of mutual interest and 
importance. 



International Education Program 



Applications for training 478 international health 
professionals from 77 countries were processed during 
FY 1975. Of these, 348 (73 percent) were for fellows from 
the World Health Organization and other affiliated agencies 
of the United Nations. Another 48 (10 percent) were for 
participants in the Department of State Cultural Exchange 
Program. The remaining 82 applications (17 percent) in- 
cluded recipients of stipends from private foundations and 
voluntary agencies (such as the Governmental Affairs Insti- 
tute, the China Medical Board, the International Planned 
Parenthood Federation, the Eisenhower Exchange Fellowships, 
and the Institute of International Education) , as well as 
those who were self-financed, sponsored by their governments, 
or referred by other federal agencies. See Tables 1 and 
2 for the distribution of such training programs, shown by 
countries of origin (arranged according to WHO regions) and 
fields of training. 

In arranging, supervising, and evaluating the U.S. 
training programs of international health professionals, 
the branch staff has developed an extensive reservoir of 
health training resources. Diligent efforts to expand these 
resources have always been made to offer the widest choices 
possible for combining individual potential and background 
with the special needs of each country. One is cognizant 
of the world's health problems by a glance at the types of 
training requested: family planning, care of the aging, 
water quality, solid waste disposal, drug abuse, venereal 
disease control, air pollution, health care delivery and 



22 



economics, nutrition, migratory labor. 

The branch is especially appreciative of the coop- 
eration extended by the various institutes not only in 
Bethesda but also in the field laboratories. The branch 
continued its assistance to other federal agencies in the 
field of health training. 

The branch again provided assistance to the World 
Health Organization in its selection of candidates from 
the United States for short-term fellowships abroad. In 
the interest of improving and expanding this country's 
health services, these fellowships are made available to 
selected U.S. citizens engaged in operational or educational 
aspects of public health. Inquiries were received from 
883 individuals, resulting in 92 applications. From these, 
45 were chosen for fellowships by the selection committee. 
Table 3 outlines the fields of training and states of 
origin of those awarded fellowships. 



23 



Table 1 



Countries Represented by International 
Health Professionals, Applications Processed During 

FY 1975 







Sponsors 




Country by WHO Region 


WHO-UN 


State 


Other 


Total 


Region I : Americas 










Argentina 
Brazil 


7 
17 




1 
1 


8 
18 


British Honduras 


1 






1 


Canada 


1 






1 


Caribbean Islands 


36 






36 


Chile 


5 




2 


7 


Colombia 


3 






3 


Ecuador 


2 




1 


3 


El Salvador 




1 




1 


French Guiana 


1 






1 


Guyana 
Honduras 


8 
1 






8 

1 


Jamaica 


2 






2 


Mexico 


10 






•10 


Uruguay 
Venezuela 


1 
11 




1 


1 
12 


TOTAL 


106 


1 


6 


113 


Region 2 : Europe 










Algeria 
Belgium 
Czechoslovakia 


1 

1 
3 


1 




1 
2 
3 


Denmark 


1 


1 




2 


France 


2 


18 




20 


Germany (Fed. Rep.) 

Hungary 

Iceland 


1 
2 




1 

1 


2 
2 

1 


Ireland 


2 






2 


Italy 
Netherlands 


2 


10 


6 


16 
2 


Norway 
Poland 


16 


2 


1 


3 
16 


Romania 


4 






4 


Spain 
Sweden 


2 


1 


2 

1 


4 
2 


Switzerland 


2 






2 


United Kingdom 


5 




1 


6 



24 





WHO 


Region 




Sponsors 




Country by 


WHO -UN 


State 


Other 


Total 


Yugoslavia 






1 


1 




2 


TOTAL 






45 


34 


13 


92 


Region 3 : 


Africa 










Ghana 






1 




1 


2 


Kenya 






2 






2 


Lesotho 






1 






1 


Liberia 










6 


6 


Mauritius 










1 


1 


Nigeria 






1 






1 


Seychelles 






1 






1 


Sierra Leone 






2 




2 


South Africa 






1 




1 


Uganda 






1 






1 


Zambia 






1 




1 


2 


TOTAL 






8 


3 


9 


20 


Region 4 : 


Eastern Mediterranean 




4 




Afghanistar 


t 




3 


7 


Egypt 






1 






1 


Ethiopia 






4 




1 


5 


Iran 






6 




1 


7 


Iraq 






3 






3 


Israel 






8 


1 


3 


12 


Jordan 






1 






1 


Lebanon 






3 






3 


Pakistan 






5 


1 




6 


Sudan 






1 




1 


2 


Tunisia 






1 






1 


Yemen 






2 






2 


Other 








1 




1 


TOTAL 






38 


3 


10 


51 


Region 5: 


Southeast As 


ia 








Bangladesh 






3 




2 


5 


Burma 








3 




3 


Ceylon (Sri 


Lanka) 


10 






10 


India 






56 


2 




58 


Indonesia 






8 




3 


11 


Nepal 






2 






2 


Thailand 






8 




10 


18 


TOTAL 






87 


5 


15 


107 



25 

Sponsors ~~ 
Country by WHO Region WHO-UN State Other Total 

Region 6: Western Pacific 

Australia 4 

Japan 1 1 

Korea 10 

Malaysia 7 

New Zealand 3 1 

Philippines 25 

Singapore 9 

Taiwan 

Vietnam 2 

Other 3 

TOTAL .64 2 29 95 



TOTAL ALL REGIONS 348 48 82 478 



2 


6 


16 


18 


2 


12 


1 


8 




4 


2 


27 




9 


4 


4 


2 


4 




3 



26 
Table 2 

Field of Training of International Health 
Professionals, Applications Processed During 
FY 1975 







Sponsors 




Field of Training 


WHO-UN 


State 


Other 


Total 


Basic medical sciences 


23 


2 


4 


29 


Behavioral sciences 


10 


2 


1 


13 


Clinical medical sciences 


33 


4 


1 


38 


Dentistry 


6 


1 


- 


7 


Environmental health and 
ecology 


132 


1 


11 


144 


Nursing 


14 


2 


7 


23 


Other biosciences 


4 


- 


3 


7 


Other health-related 
professional fields 
Drug abuse 
Epidemiology 
Family planning 
Health administration 
Hospital administration 
Pharmacy 

Veterinary medicine 
Mental health 
Other 


18 

26 

14 

10 

2 

2 

6 

1 

8 


1 

5 
18 

1 

10 


1 

2 

12 

10 

18 

5 


20 

28 

26 

25 

38 

3 

6 

1 

23 


TOTAL 


87_ 


35_ 


48 


170 


Paramedical technologies 
Clinical 
Environmental 
Public health 


2 

1 
13 


- 


2 

1 


4 

1 

14 


TOTAL 


16 


_ 


3 


19 



Physical sciences 
Sanitary Engineering 
Statistics 
Other 

GRAND TOTAL 



7 


- 


- 


7 


11 


- 


- 


11 


5 


1 


4 


10 


348 


48 


82 


478 



27 



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28 



Gorgas Memorial Institute 

This institute was founded in 1921 as a living mem- 
orial to Major General William Crawford Gorgas, whose 
efforts in environmental sanitation led directly to the 
successful construction of the Panama Canal and to the 
virtual eradication of yellow fever from the great urban 
centers of tropical America. With continuous direct sup- 
port from Congress since 1929, the institute has operated 
the Gorgas Memorial Laboratory in Panama City, Republic of 
Panama. Support of the research and training activities 
of the Gorgas laboratories comes from the Congressional 
appropriation, philanthropic donations, and research grants 
awarded by various agencies of the U.S. Government, 
especially the Public Health Service and the Army. The 
laboratories are one of the few research centers located 
in a near tropical area that possesses modern facilities 
and a well-trained staff. Another factor promoting the 
laboratory activities is the fact that the Gorgas Institute 
is an international organization capable of entering into 
cooperative arrangements and studies with authorities and 
investigators in any of the countries of the Western hemi- 
sphere. Capitalizing on these characteristics the program 
of the Gorgas laboratories has been devoted to research 
investigations of human disease, training scientists in 
tropical medicine, disease surveillance, and collaboration 
in international health efforts. 

From its inception, the laboratory has concentrated 
its efforts toward the investigation and control of a 
variety of infectious diseases of particular tropical sig- 
nificance. Economic and social evolution has resulted in 
changing disease patterns, which requires broadening the 
scope of research activities of this laboratory. Thus, in 
addition to studies of vectorborne disease, major emphasis 
must be placed on enteric infections, nutritional derange- 
ments , and other human health problems influenced by geo- 
graphic, environmental, genetic, and social factors. 

In 197 the Fogarty International Center assumed 
responsibility for the congressional justification of 
institute programs and, subsequently, encouraged a new 
interest in scientific advisory activities relating to pro- 
gram review and development. In 1972 the institute acquired 
responsibility for the operation of the Middle America 
Research Unit (MARU) a former field laboratory of the 
National Institute for Allergy and Infectious Diseases 
located in Ancon, Canal Zone. During its 16-year history, 
MARU has gained wide international respect for its work 
on such diseases as hemorrhagic fever, equine encephalitis, 
and hepatitis of several Latin American countries. Al- 
though MARU operations are now financed by annual contracts 
with NIH, the Gorgas Memorial Institute has already effected 
a consolidation of all its virological work at MARU. 



29 



Bilateral Agreements for Cooperation in Biomedical Research 

In FY 1969, efforts were initiated to expand coop- 
eration with other governments , involving biomedical 
research. This new effort involved programs for collab- 
oration within existing or newly negotiated bilateral 
general science agreements. While deliberately drafted 
to embrace a wide spectrum of scientific areas, these 
programs encourage cooperating governments to share the 
cost of research. Expenditures in the cooperating country 
would be paid for by that government and those in the 
United States by the American Government. Over the past 
several years these arrangements provided additional 
vehicles to utilize that reservoir of scientific and 
technical biomedical personnel abroad who have contributed 
to the advancement of the world's biomedical knowledge. 

These bilateral agreements in science and technology 
generally developed from a mutual desire to cooperate. 
A visit to the country in question by a team of special- 
ists representing science and technology usually initiated 
the negotiation of the agreement. 

Since these arrangements are very general in nature, 
the Department of State usually designated one agency, 
such as the National Science Foundation, of the United 
States Government to act as overall "executive agency" in 
coordinating implementation of these accords. If a 
cooperative biomedical research project is developed by 
a participating agency such as NIH under such a general 
agreement, the project application is submitted to the 
United States executive agency and its foreign counter- 
part agency for approval. 

To date, under the aegis of these governments, a 
number of biomedical cooperative projects have been pro- 
posed and several exchanges of information and personnel 
have taken place between U.S. and foreign biomedical 
laboratories. Although much informal collaboration con- 
tinued on the scientist-to-scientist level in a large 
number of the countries with which United States scientists 
have contacts, formal cooperative activities in the bio- 
medical and health sciences were limited to relatively 
few. The countries involved in these general cooperative 
agreements for FY 1975 were France, Italy, and Japan. 

France 

The U.S. -France Agreement for Scientific and 
Technological Cooperation is administered by the U.S. 
Department of State and the French Ministry of Foreign 
Affairs. Many U.S. executive agencies participate in the 
agreement. The National Institutes of Health collaborate 
with their counterpart agency, the Institut National de 



30 

la Sante et de la Recherche Medicale (INSERM) on seven 
research projects: 

1. Biological, Immunological and Biomedical Studies 

of Viruses Associated with Leukemia and Solid Tumors 

U.S. Investigator: Dr. J. B. Moloney, NCI 
French Investigator: Prof. G. Mathe , Hopital Paul 

Broussee, Villejuif 

2. Basic Reactions of Pulmonary Tissues to Inhaled 
Pollutants 

U.S. Investigator: Dr. Claude J. M. Lenfant, NHLI 
French Investigator: Prof. P. Sadoul , Unite de 

Recherches de Physiopathologie 

Respiratoire , Nancy 

3. Cellular Micro-Irradiation, Experimental Ultra- 
structural 

U.S. Investigator: Dr. W. N. Jensen, George Washington 
University and Dr. G. Brecher, 
University of Calif., San Fran. 

French Investigator: Prof. M. Bessis, Institut de 

Pathologie Cellulaire, Bicetre, Paris 

4. Hormones and Cancer 

U.S. Investigator: Dr. E. V. Jensen, Director, Ben 

May Lab. for Cancer Res., Chicago 
French Investigator: Prof. E. E. Beauiles, Hopital 

de Bicetre , Paris 

5. Myeloma Proteins 

U.S. Investigator: Dr. Henry Metzger, NIAMDD 
French Investigator: Prof. M. Seligman, Hopital 

St . Louis , Paris 

6. Perinatology and/or Pregnancy and Maternal Health 

U.S. Investigator: Dr. Norman Kretchmer, NICHD 
French Investigator: Prof. A. Minkowski, Cochin 

Maternity Hospital, Paris: 
P. Royer , Paris, and others 

7. Thyroglobulin Synthesis 

U.S. Investigator: Drs. J. E. Rail, J. Robbins and 

J. Wiff, NIAMDD 
French Investigator: Prof. S. Lissitzky, Faculte de 

Medicine, Marseilles 



31 



Collaboration involves primarily exchanges of information. 
However, three scientists from each side on each project 
may spend up to 3 months in the other country's collabora- 
ting project laboratories. 

In the fall of 1974, when President Giscard D'Estaing 
of France and President Ford met in Martinique, it was 
agreed that cooperation in biomedical research should be 
expanded. Subsequently, through a series of visits by 
administrators on both sides, it was agreed to expand 
cooperation, including the establishment of a strategy 
committee for expanded cooperation in cancer research 
beyond that already carried out under the agreement. 

Following the visit to V. 7 ashington in June of 1975 
by Mme. Simone Veil, the French Minister of Health, there 
was an exchange of views between Secretary Weinberger and 
Mme. Veil expressing joint support for the expansion of 
U.S. and French cooperative activities in cancer research 
through the INSERM-NIH agreement and giving approval to 
the proposal for the creation of a Strategy Committee. 

Italy 

The United States-Italy Science Agreement, signed in 
1967, is a general "umbrella" agreement for scientific 
cooperation within which specific biomedical projects have 
been incorporated since FY 1970. During FY 1975, as with 
previous years, several ongoing and new projects were 
recommended by the National Science Foundation to be 
included within the above "umbrella" agreement. These 
projects, the principal researchers, including those projects 
now incorporated within the "umbrella" agreement and those 
pending approval either by U.S. agencies or the Conseglio 
Nazional delle Recherche are listed below under the 
institute through which they derive support. 



NCI 



Immune Response of Mice Against Experimental Leukemia 

U.S. Investigator: Dr. Gustavo Cudkowicz, State 

University of N.Y. 
Italian Investigator: Dr. Enzo Bonmassar, University 

Of Naples 

Characterization of the Viral Genome Products (RNA and 
Proteins) Expressed by Cells Transformed by Mammalian 
RNA Tumor Viruses 

U.S. Investigator: Dr. Maurice Green, St. Louis U. 
Italian Investigator: Dr. Giancarlo Vecchio, Uni- 
versity of Naples 



32 



3. Antigenic and Chemical Characterization of Cells 
Transformed by Adenoviruses 

U.S. Investigator: Dr. Fred Rapp, Penn . State U. 
Italian Investigator: Dr. Sergio Pauluzzi, University 

of Peruzio 

4. The Role of Cyclic Nucleotides, in the Regulation of 
Gene Expression and Protein Synthesis in Animal Cells 

U.S. Investigator: Dr. Ira Pastan, NIH 
Italian Investigator: Dr. Stelio Varrone , University 

of Naples 

NHLI 

1. Development of Physico-chemical Techniques of Bio- 
logical Interest 

U.S. Investigator: Dr. R. L. Berger, NHLI 
Italian Investigator: Dr. L. Rossi-Bernardi , Univer- 
sity of Milan 

2. Basic Mechanisms Underlying Erythropoiesis 

U.S. Investigator: Dr. Albert S. Gordon, New York 

University 
Italian Investigator: Dr. Cesare Peschle, University 

of Naples 

3. Relationship Between the Metabolism of Triglycerides 
and Myocardial Function 

U.S. Investigator: Dr. Marilyn E. Hess, University 

of Penn. 
Italian Investigator: Dr. Adalgisa Bizzi & Silvio 

Garattini 

4. Bioengineering Analysis of Microvascular Function 

U.S. Investigator: Dr. Marcos Intaglietta, University 

of Calif., San Diego 
Italian Investigator: Dr. Rodolfo Monti, University 

of Naples 

5. Hemoglobin and Myoglobin Kinetic Studies 

U.S. Investigator: Dr. J. Parkhurst, University of 

Nebraska 
Italian Investigator: Dr. Giuseppe Geraci , University 

of Rome 



33 



6. Chemistry, Morphology, and Biological Activity of the 
Pulmonary Surfactant System in the Fetus and Adult, 
Normal and Abnormal 

U.S. Investigator: Dr. Emile M. Scarpelli, Yeshiva 

University 
Italian Investigator: Dr. Ermelando Cosmi , University 

of Rome 

7. Patterns in Respiratory Control in Human Shock 

U.S. Investigator: Dr. John H. Siegel, SONY 
Italian Investigator: Dr. G. C. Castiglioni, CNR 

8. New Modifications for Mechanical Ventricular Assis- 
tance 

U.S. Investigator: Dr. David B. Skinner, Johns 

Hopkins University 
Italian Investigator: Dr. Sergio Stipa, University 

of Rome 

NIAMDD 

1. Biochemical and Genetic Studies on the Structure of 
Histidyl-tRNA Synthetase and Methylation of Histidine- 
tRNA 

U.S. Investigator: Dr. Bruce N. Ames, University of 

California, Berkeley 
Italian Investigator: Prof. Francesco Salvatori and 

Francesco de Lorenzo, University 

of Naples 

2 . Mechanisms of Glucose Transport and the Action of 
Insulin 

U.S. Investigator: Dr. Pedro Cuatrecasas , Johns 

Hopkins University 
Italian Investigator: Prof. Gennaro Illiano, Uni- 
versity of Naples 

3. Mechanism of Repression of Biosynthetic Pathways: 
the Histidine Operon 

U.S. Investigator: Dr. Robert F. Goldberger, NIH 
Italian Investigator: Dr. G. B. Bruni , University 

of Naples 

4. Purification and Characterization of Human Glycosidases 
and Study of their Possible Structural Alterations 

in Sphinglipidoes 

U.S. Investigator: Dr. Y. C. Lee, Johns Hopkins U. 
Italian Investigator: Dr. G. Romeo, University of 

Naples 



34 



5. Metabolic Effects of Acid-Base Disorders 

U.S. Investigator: Dr. Arnold S. Relman, University 

of Pennsylvania 
Italian Investigator: Dr. A. Tizianello, University 

of Genoa 

NINCDS 

1. Central Control of Neuromuscular Apparatus and Motor 
Coordination 

U.S. Investigator: Dr. Emilio Bizzi, MIT 
Italian Investigator: Dr. Vincenzo Tagliasco, Uni- 
versity of Genoa 

Japan 

During FY 1975 the U.S. -Japan Cooperative Science 
Program, established in 1960 to foster a closer collabora- 
tion between scientists of the two nations , included within 
its program nine biomedical research projects listed 
below : 

1. The Development of Pharmacological Probes for Studying 
the Cating Mechanism of Nerve Excitation 

U.S. Investigator: Toshio Narahashi , Duke University 

Medical Center 
Japanese Investigator: Issei Seyama, Hiroshima 

University School of Medicine 

2. Reversible Interactions of Molecular Oxygen with 
Cobalt Porphyrin Complexes and their Apohemoprotein 
Complexes 

U.S. Investigator: Takashi Yonetani, University of 
Penn. and 3 others 

Japanese Investigator: Takao Kwan , University of 

Tokyo and 4 others 

3 . Biomembrane Formation and Function in Tetrahymena 

U.S. Investigator: Guy A. Thompson, University of 

Texas - Austin 
Japanese Investigator: Yoshinori Nozawa, Gifu Uni- 
versity School of Medicine 

4. Central Mechanisms of Motor Control 

U.S. Investigator; Dr. Hiroshi Asanuma, Rockefeller 

University 
Japanese Investigator: Dr. H. Shimazu, University 

of Tokyo 



35 

5. Development and Total Synthesis of Physiologically 
Active Natural Products 

U.S. Investigator: Dr. Lester A. Mitscher, Ohio State 

University 
Japanese Investigator: Dr. Tetsuji Kametani, Tohoku 

University 

6. Biochemical Studies on Biologically Active Complex 
Carbohydrates 

U.S. Investigator: Roger W. Jeanloz, Harvard University 
Japanese Investigator: Tamio Yamakawa , University 

of Tokyo 

7 . Effects of Perinatal Exposure to Endocrine and 
Oncogenic Factors 

U.S. Investigator: Howard A. Bern, University of 

Calif . , Berkeley 
Japanese Investigator: Noboru Takasugi, Okayama 

University 

8. Amplification of Eukaryote DNA Fragments 

U.S. Investigator: Bruce M. Alberts, Princeton 

University 
Japanese Investigator: Kenichi Matsubara , Kyushu 

University 

9. The Optical Properties and Structure of Deoxyribo- 
nucleic Acid by Electric Dichroism Techniques 

U.S. Investigator: Elliot Charney , NIH 
Japanese Investigator: Kiwamu Yamaoka , Hiroshima 

University 

Geographic Health Studies 

As suggested by the bilateral programs, the scientists 
and science administrators of the National Institutes of 
Health are actively seeking to expand their knowledge of 
foreign health activities and programs to provide new 
insights for improving the health of the American people. 
Important elements of all health activities, of course, 
include biomedical research, medical education, health 
manpower and health services. An analysis of these foreign 
health-related activities and programs may provide the 
U.S. Government health administrators with new insights in 
solving some of the complex problems relating to the 
improvement of health in the United States. 

Recognizing the cultural and other historical influence 
upon foreign medical systems, no single country or govern- 
ment may have the type of medical care or health system 



36 

which will provide completely adequate health assistance 
desired by our citizens. A study of the best feature of 
foreign health systems, however, ultimately may provide a 
better understanding of the perspective within which health 
exists in the United States. Such a perspective, however, 
must include an improved comprehension of the political, 
economic, social, and other cultural aspects of society 
itself. 

The Fogarty International Center, the first advanced 
study center of its kind within the Federal Government, 
therefore, is attempting to make information on the health 
systems of other countries as widely available as possible 
to both the pluralistic influences in the public and 
private sectors affecting the decision making processes in 
the United States. This information is also freely 
available to the medical communities and governments of 
other countries and international organizations. The 
specific objectives of these studies are: 1) To advance 
U.S. knowledge of health practices in different geographic 
regions or individual countries of Europe, South America, 
Asia, Africa and Australia; 2) To publish selected documents 
covering all phases of medicine and health in these 
different regions; and 3) To improve cooperation between 
clinicians, health scientists, and health administrators 
in the United States and other geographic areas . 

The scope of the project may be divided into the 
following areas. Biomedical research : 1) The overall 
philosophy and organization of biomedical research; 2) 
Research trends and priorities; 3) Objectives; 4) Resources 
available; 5) Relationship to medical care. Interface 
Between Research and Education and Training : 1) The 
education of both professional and para-professional health 
manpower in general; 2) The role of the medical school; 

3) The effect of health care needs upon medical education; 

4) The financing of medical education; 5) The influence of 
public and private organizations upon medical school 
curricula. Interface Between Research and The Delivery of 
Medical Care : 1) The organization of health care systems; 
2) Respective roles of public and private sectors in 
improving health; 3) The economics of health; 4) Special 
services to population groups such as mothers and children; 

5) Geriatrics; 6) Mental health. 

During FY 197 5 a number of publications were prepared 
within the aegis of the Center's Geographic Health Studies: 

Soviet Personalities in Biomediclne 

This comprehensive volume, compiled in accordance 
with an interagency agreement between the Fogarty Inter- 
national Center and the Library of Congress, is considered 
a most valuable tool in furtherance of contact between 
American and Soviet biomedical research scientists. Listed 



37 



are 6,155 Soviet personalities associated with medicine 
and health-related research, their date and place of birth, 
education, specialization, career positions, professional 
activities, honors and awards, publications and other 
significant data. The personalities identified are those 
considered most likely to be involved in exchanges in 
fields of interest to the United States under the terms 
of existing and future agreements. 

Soviet Biomedical Institutions: A Directory 

The companion volume to Soviet Pers o nalities in 
Biomedicine (above) , this also was assembled by the 
Library of Congress under the interagency agreement. Its 
purpose is to provide United States biomedical scientists 
with a guide to the organization, personnel, geographic 
distribution, subordination, and research activities of 
selected Soviet medical and biological institutions. 
Described are some 1,200 institutions, including research, 
education and service facilities, and learned societies. 
Among the research facilities listed are institutes, 
independent laboratories , and research and treatment centers 
Health care facilities included are hospitals, polyclinics, 
and dispensaries. Educational organizations listed include 
medical training institutes, university faculties of 
medicine and the military medical academy. Medical 
societies on the All-Union level are also included. The 
directory's detailed descriptions of Soviet facilities 
are considered most important toward the exchange of in- 
formation, personnel and delegations under the expanded 
Agreement for Cooperation of 1972 and future agreements 
of this type. 

A Barefoot Doctor's Manual 

Translated from the Chinese publication of like title 
issued in September 1970 by the Institute of Medicine 
of Hunan Province, this volume has been issued for limited 
circulation in the United States. Its focus is upon 
improvement of medical and health care facilities in rural 
Chinese villages, with its primary purpose integration 
of the following: prevention and treatment; disease and 
symptoms, with stress on disease; traditional Chinese and 
Western medicine; the native and foreign; mass production 
and quality improvement. By delineating these principles 
and addressing the actual conditions at the rural level, 
the manual is aimed at meeting the working needs of the 
sub-professional "barefoot doctors" serving the broad 
rural population. Publication of this translated manual 
is toward further investigation and a better understanding 
of Chinese medicine and methods. 

Soviet Research in Pharmacology and Toxicology 

It is believed vitally important that workers in the 



38 

fields of pharmacology and toxicology be kept informed 
upon drug studies being conducted in other countries, and 
this publication is deemed valuable toward this end. The 
author, Dr. William H. Fitzpatrick, having expert famil- 
iarity with Soviet literature, has included 675 references, 
and there is also a comprehensive index making the volume 
an excellent reference text. It should prove of special 
interest to those concerned with drug research and develop- 
ment, in addition to those with a more general interest 
in the subjects covered. 

China Medicine As We Saw It 

Recognized by reviewers as another step toward filling 
in the spaces of the Chinese medical puzzle, this anthology 
of personal reports by professionals is the first such 
volume by recent visitors to the People's Republic of China. 
Reported on in 15 chapters are Chinese innovations in 
health; public health; its organization and status; public 
health practices; prevalent diseases; and biomedical 
research. Covered is a variety of subjects including: 
traditional and modern medicine, limb reattachment, 
acupuncture, fracture management, family planning, food 
and nutrition, occupational health, and the special 
significance of nasopharyngeal cancer in China. The volume 
is illustrated, and has several tables and an index. 

Chinese Herbal Medicine 

The author of this work, Dr. C. P. Li, is a distin- 
guished Chinese-born scientist, who also was responsible 
for Anticancer Agents Recently Developed in the People's 
Republic of China , published earlier by the Fogarty 
International Center. Documented in this new volume are 
the practices of the Chinese utilizing medicinal herbs, 
resulting from an intensive study carried out by Dr. Li 
with the approval of the People's Republic of China. 
Included is an illustrated pharmacognosy of 44 individual 
herbs discussed in the monograph. It is believed that this 
work will prove helpful in further scientific investigation 
and toward a fuller understanding of the subject. 

A Bibliography of Chinese Sources on .'.Medicine., and 
Public Health in the People's Republic of China: 
1960-1970 

This volume was also compiled by the Library of Congress 
by means of an interagency agreement with the Fogarty 
International Center. No fewer than 15,000 entries cover 
articles in journals and newspapers, and monographs. These 
are categorized under several headings including: acu- 
puncture and moxibustion; allergy; anesthesiology; cardio- 
vascular diseases; dentistry and oral surgery; dermatology; 
endocrinology, metabolism and nutrition; gastroenterology; 
hematology; infectious diseases; neurology; obstetrics and 



39 

gynecology; and 20 others. 

Chinese Personalities in Biomedicine 

The information contained in this publication was 
also assembled by the Library of Congress under the inter- 
agency agreement, using the same public sources as used 
for the Bibliography of Chinese Sources on Medicine and 
Public Health in the People's Republic of China: 1960- 
1970 (above) . These sources comprise medical and related 
journals published by the PRC. In addition to listing 
the names of those prominent in Chinese biomedicine, the 
volume also provides data on their education, appointments, 
specializations, publications, memberships, and much other 
pertinent information. 

Acupuncture Anesthesia 

This publication is a translation from the Chinese 
volume of the same title, produced in November 1972 by a 
Shanghai-based editorial and writing team at the request 
of the Ministry of Public Health of the People's Republic 
of China. Acupuncture anesthesia is a comparatively 
recent development that has found increasing use and 
success since the time of the Cultural Revolution. This 
English-language version has been produced for limited 
circulation to scholars having a general or specialized 
interest in this aspect of health care. 

Acupuncture Anesthesia in the People's Republic o f 
China, 1973 

Acupuncture anesthesia and therapeutic acupuncture 
are subjects that since 1970 have piqued the interest of 
the American public and the American medical profession. 
This volume, written by Dr. James Y. P. Chen, a Chinese- 
educated scientist-clinician with a distinguished American 
background, is intended to provide Americans with an over- 
view of acupuncture anesthesia. During a visit to the 
PRC in 1973, Dr. Chen had opportunities to observe 30 
operations performed under acupuncture anesthesia and to 
discuss this and other aspects of health care with 
numerous Chinese scientists, physicians, and other health 
professionals. The publication covers many aspects, 
including a summary of experience with this modality in 
the West, the selection and preparation of patients, 
selection of acupuncture points, application techniques, 
and the intra-operative and post-operative management of 
the patient. 

Respiratory Research in the People's Republic of 
China 

The current state of knowledge of pulmonary medicine 
reflects the contributions of scientists and physicians 



40 - 

working in many countries. The flow of information from 
the People's Republic of China was interrupted for many 
years, but it is now evident that there is much to learn 
from Chinese pulmonary medicine. Many pulmonary diseases 
are related to local ecology, and it is well known that 
some aspects of physiologic function may differ among 
ethnic groups. It is therefore considered fortunate that 
Dr. Frederick F. Kao, eminent respiratory physiologist and 
Professor of Physiology at State University of New York 
undertook to study the contributions of Chinese research 
in the field of respiration, and as a result prepared this 
monograph reviewing the many facets of pulmonary research 
and medicine in the PRC. 

Urban Emergency Medical Service of the City of 
Leningrad 

Translated from the Russian work of M. A. Messel, this 
publication discusses in detail the development and work 
of emergency medical services in the USSR, with particular 
emphasis upon the system prevailing in Leningrad. Described 
are the operation of central and district stations, methods 
of recording the stations' activities, the work of the 
station physician, volume of medical aid rendered, and the 
physician's tactics and operational methods. Also dealt 
with are the prevention of accidents, and the role of the 
station as an evacuation unit. The comprehensive volume 
contains many illustrations and tables. 

An Economic Analysis of the Cooperative Medical 
Services in the People's Republic of China 

The economics of cooperative medicine in the PRC 
comprise the main theme of this monograph by Teh-wei Hu, 
Visiting Research Professor at the Fogarty International 
Center. Much light is thrown upon the manner in which, 
in 8 years, the PRC established medical services relevant 
to basic medical needs and an effective medical system. 
The promotion of herbal medicine and the utilization of 
"barefoot doctors" are described as cost minimization 
approaches with great effect upon the economics of such 
a medical system. The publication has relevance as a 
study of interest for American specialists in the field 
of public health and the provision of medical services. 

The Center as a Coordinator for NIH International Activities 

For a number of hears NIH has sought the collaboration 
and scientific productivity of foreign scientists in ful- 
filling its mission of improving the health of the people 
of the United States and in contributing to the base of 
scientific knowledge upon which American scientists depend. 
The continuing limitation on the worlds resources, of 
course, have accentuated the NIH intent to utilize out- 
standing research opportunities regardless of geographic 



41 

location. Several different mechanisms are used to 
maximize benefit from these international resources, 
including grants and contracts to foreign institutions, 
publication of biomedical data derived from reports from 
abroad, and information from NIH participants in inter- 
national scientific conferences and symposia. Thus, in 
addition to its other programs discussed above, the 
Fogarty International Center performs a coordinating role 
in making available for use of the NIH scientific 
community biomedical data derived through the aforementioned 
and other mechanisms. 



II 



INTERNATIONAL COOPERATION IN THE HEALTH 
SCIENCES BY COMPONENTS OF NIH 



In addition to the activities in the international 
health sciences coordinated by the Fogarty International 
Center, many other components of NIH participate in 
international programs, projects, and other activities 
designed to promote the biomedical sciences. These 
include cooperation with national and international 
organizations throughout the world. The following 
summaries of the more important aspects of these coopera- 
tive efforts afford some measure of insight into these 
activities. 



43 



NATIONAL CANCER INSTITUTE 



Since the passage of the National Cancer Act in 
1971, the international activities of the National 
Cancer Institute (NCI) have been directed toward the 
development of a more coordinated program of international 
cooperation in cancer research and clinical care of the 
cancer patient. The interrelationship that has been 
established between the NCI and international institutions 
and organizations certainly will be mutually beneficial 
to all concerned, particularly since programs of inter- 
national cooperation provide opportunities to immeasurably 
broaden our understanding of cancer cause and cancer pre- 
vention. For instance, variations in incidence rates 
for different types of cancer throughout the world are 
indicative of the role of geographic, social, and other 
environmental factors in their development. Thus 
"pooling" international efforts against cancer could more 
rapidly result in the synthesis of a comprehensible whole 
from those unique international components that might 
otherwise continue in diverse directions for a much 
longer period of time and with unnecessary expenditure of 
economic resources. Perhaps the greatest benefit to NCI, 
the national cancer program, and, ultimately, the cancer 
patient, is the sharing of international cancer research 
resources, particularly the resource of scientific intellect 
and its product of meaningful information. 

During FY 1975, the Office of International Affairs 
within the Office of the Director, NCI, continued its 
effort of implementing the programmatic goals set forth 
in the act of 1971, as amended in 1974. A major effort 
has been devoted to developing a cohesive method for 
utilizing the cancer expertise that exists outside of the 
United States. Emphasis has been placed on accumulating 
all available data on cancer problems, analyzing that data, 
and disseminating it throughout the world anticipatory 
of such information serving as a data base for developing 
a comprehensive international program of collaborative 
cancer research. 

International Cancer Research Data Bank 
Program 

Soon after the enactment of the National Cancer 
Act, NCI established an International Cancer Research 
Data Bank (ICRDB) Program. During its first 2 years of 
activity the information needs of the cancer research 
community were identified, existing information systems 
described, and a scientific information system designed. 
Ultimately, a detailed plan evolved for the operation of 
this program. 

45 



46 



Subsequently, a series of contracts were awarded for 
its implementation. The contracts - the majority initiated 
in FY 1975 - include efforts for (1) the rapid screening of 
1,000 biomedical journals and other literature sources 
for all articles related to cancer, (2) preparation 
of abstracts of the cancer-related articles, (3) conversion 
of abstracts to magnetic tape and related data-processing 
operations required to produce and improve the ICRDB Data 
Base, (4) collecting descriptions of currently active 
cancer research projects from scientists located in 
research centers around the world, and (5) technical 
support to provide many special services needed by the 
ICRDB program. 

The more than 46 , 000 abstracts describing recent 
results of cancer-related research and current cancer 
research activities are made available with ease -to 
scientists and clinicians through on-line computer termi- 
nals located at more than 400 academic and research centers 
throughout the United States and, increasingly, in other 
countries. Using any combination of words or terms in 
the title, text, or index field, scientists can retrieve 
abstracts dealing with a specific cancer topic. The 
entire text of the retrieved abstracts can be viewed at 
a computer terminal or printed and mailed to the scientists. 
The system, which uses the MEDLARS computer system of the 
National Library of Medicine (NLM), is funded by an inter- 
agency agreement between NCI and NLM. 

Concurrent with literature screening and abstracting 
is the collection and processing of approximately 10,000 
brief descriptions of existent cancer research projects, 
including short outlines of cancer therapy protocols. 
This task is performed in the Current Cancer Research 
Project Analysis Center (CCRESPAC) of the Smithsonian 
Science Information Exchange, one of the ICRDB program 
contractors. These abstracts are then made available for 
on-line searching through the CANCERLINE network. In 
addition, CCRESPAC will offer another information product 
by producing some 30 technical bulletins listing current 
research projects in specific narrow subject areas. The 
bulletins will be distributed to scientists working on 
the same specific topic in order to establish direct 
communication with these colleagues. 

At present, the ICRDB program is implementing and 
operating four Cancer Information Dissemination and 
Analysis Centers (CIDACs) . These receive inquiries 
from comprehensive cancer centers, academic institutions, 
private laboratories, individual researchers, clinicians, 
and scientists throughout the world for the latest infor- 
mation on a subject. CIDAC subject specialists query the 
CANCERLINE data base, review the output, select relevant 
abstracts, and forward the results of the search to the 
user. This output includes not only the published litera- 



47 

ture available in CANCERLINE but also all ongoing research 
projects in the data base. 

CANCERLINE can be accessed on an "as-needed" basis 
to respond to requests by the phone, mail, or personal 
visit. Conversely, CIDACs will function as a 
viable organization to stress the active dissemination of 
cancer research information by automatically distributing 
a steady stream of abstracts in specific subject areas 
to scientists working in those areas as a part of a program 
for the Selective Dissemination of Information (SDI) . 
Current abstracts dealing with very narrow cancer subject 
areas will be sent to researchers working in those areas 
on a regular basis. Technical bulletins, each containing 
abstracts covering several years of results in a specific 
cancer research area, will also be published and forwarded 
to users. The inquiries, as well as the current awareness 
SDI products and technical bulletins, will all be obtained 
by computer searches of the CANCERLINE data base. 

Other current, active ICRDB projects include (1) 
an International Registry of Tumor Immunotherapy 
Protocols containing descriptions of over 200 clinical 
trials of new immunotherapeutic procedures for treating 
cancer; (2) an International Cancer Epidemiology Clearing- 
house that is funded jointly by ICRDB, the International 
Agency for Research on Cancer (IARC) in France, and 
the German Cancer Research Center in Heidelberg; (3) 
a contract with the International Union against Cancer 
(UICC) for support of the Committee for International 
Collaborative Activities (CICA) that promotes cooperation 
between cancer centers around the world, serves as an 
international advisory group for the NCI, and is assisting 
in the development and dissemination of ICRDB program 
products and services throughout the world; (4) a project 
with UICC to collect data on cancer therapy protocols from 
countries outside the United States; (5) the preparation 
of a directory listing and describing more than 1,000 
cancer research organizations in countries around the 
world; (6) support of development of an improved 
international classification of diseases (ICD-(0)) for 
coding clinical cancer data under the auspices of the 
World Health Organization; and (7) support of a new 
program to collect information about cancer research 
projects and results in Latin America. 

COOPERATIVE RESEARCH 

Cooperative cancer programs are in effect with a 
number of foreign nations either as bilateral agreements 
between governments or formal agreements between the 
National Cancer Institute and a scientific institute or 
society of a foreign country. 



48 



U.S.-U.S.S.R. 

Established by the 23 May 1972 U.S.-U.S.S.R. 
Agreement for Cooperation in the Fields of Medical 
Science and Public Health, American-Soviet cooperation 
is beginning to show dividends in almost all of the six 
cancer problem areas agreed to for joint study. 

1. Cancer Chemotherapy 

During the Third Working Meeting of U.S.-U.S.S.R. 
chemotherapists, April 1975, the status of clinical 
and experimental studies on 49 American and 66 Soviet 
drugs exchanged to date was examined. The results were 
considered impressive, especially with the U.S. nitro- 
soureas, hexylmethylmelamine, and DTIC; the Soviet's 
ftorafur and asaley,- adriamycin from Italy; and the antra- 
cycline antibiotics from both countries. U.S. use of asaley 
and ftorafur, for example, has revealed preliminary clini- 
cal efficacy of ftorafur against adenocarcinoma of the 
gastrointestinal tract. Because of its decreased side 
effects, ftorafur (an analog of 5-f luorouracil) may 
prove to be effective clinically as a single therapeutic 
agent or when used in combination with other anticancer 
agents. Asaley is also showing some clinical promise, in 
selected cancers. 

Detailed analyses of these data will be the primary 
content of a monograph, The Development of Drugs for 
the Treatment of Cancer , being prepared jointly. This 
monograph and another, Cancer of the Lung , are in final 
review for publication. 

Both sides are continuing patient accrual in joint 
studies of lung cancer utilizing surgery with or without 
CCNU as the modes of therapy, continuing studies of 
epidermoid carcinoma, and undertaking pilot studies 
jointly on the efficacy in small cell carcinoma of the 
drug combination adriamycin-DTIC-vincristine. 

Agreement was reached to organize a joint conference 
on ovarian cancer to exchange generalized experiences of 
both countries. It was agreed, as well, that for 
experimental purposes one or two new , potential anticancer 
drugs would be exchanged per year. There will be, in 
addition, an active exchange of drugs of synthetic and 
natural origin. 

2. Cancer Immunology 

During the second working meeting of U.S.-U.S.S.R. 
immunotherapists, April 1975, the present status of 
collaborative trials indicated that an impressive number 
of patients have been entered into the trials. The 



49 



Soviet results, especially those combining chemotherapy 
and immunotherapy, show considerable promise in the clini- 
cal management of metastatic melanoma. 

An important feature of this meeting was the agree- 
ment to hold a conference on "Fetal and Tumor Antigens" 
in the Soviet Union in 1975 to permit an intense exchange 
of research information. This conference also provides 
to many young Soviet scientists the opportunity for 
active participation, as well as exposure to the most 
recent advances being made by Americans working in the 
broad interdisciplinary field of fundamental and applied 
immunology. 

3. Cancer Virology 

In the third working meeting of the U.S.-U.S.S.R. 
cancer virologists, May 1975, discussion focused on 
the following results: (1) isolation of a group of 
"potentially" oncogenic viruses from human cell lines in 
continuous culture by both U.S. and U.S.S.R. scientists; 
(2) isolation of "candidate" oncogenic viruses of the 
herpes group and type C oncornaviruses from two species 
of nonhuman primate inoculated with materials from 
leukemic humans; and (3) isolation and study of a virus 
associated with leukemia in cattle. These and other 
findings were reported during a 2-day symposium entitled, 
"Viral Neoplasia in Animals and Man." 

4. Mammalian Somatic Cell Genetics Related 

to Neoplasia 

When this working group met for the second time in 
June 1974, in Moscow, a symposium was held- "Mammalian 
Somatic Cell Genetics Related to Neoplasia." Five 
American and 11 Soviet papers were presented. Abstracts 
of the papers have been published in Russian in the Soviet 
journal, Genetika. A summary of the symposium will be 
published in the Journal of the National Cancer Institute . 

Although it was agreed then to continue the program of 
cooperation as constituted during the first meeting, the 
anticipated scientific momentum has not appeared yet. 

5. Cancer Epidemiology 

During the second working meeting convened in Febru- 
ary 1975, two important agreements were reached as a re- 
sult of the information exchanged: A monograph will be 
published jointly on the current state of cancer epidemi- 
ologic research in the United States and the Soviet 
Union, and a joint study will be undertaken of the 
epidemiology of cancer of the breast. 

Acknowledging the invitation of the U.S.S.R. 



50 



coordinator, a delegation of American epidemiologists 
spent October 5-18, 1975, in the Soviet Union exchanging 
information with Soviet cancer epidemiologists and visiting 
Soviet institutes engaged in cancer and cancer-related 
epidemiologic research. The primary objective was the 
design and development of a protocol for conducting 
the joint project on the epidemiology of cancer of the 
breast. 

6. Cancer Control and Cancer Centers 

Resulting from the second working meeting in Lenin- 
grad in May 1975, there was agreement to pursue several 
areas jointly: (1) the most effective means of early 
detection of breast cancer; (2) objectives and methodology 
essential to the rehabilitation of patients with breast 
cancer; (3) efficacy of cancer therapy (end results) 
using breast cancer as the model; and (4) the role of 
U.S. cancer centers and Soviet oncologic institutes in 
cancer control activities and their organization for 
oncologic research, both fundamental and clinical. This 
working group is expected to work in consonance with the 
specialists in cancer epidemiology. 

Interestingly, joint projects to study cancer of the 
breast are included in five of the six problem areas, 
genetics being excepted. 

Scientist Exchange 

Twenty-six Soviet cancer specialists visited the NCI 
and other cancer centers in the United States for a 
total of 23.30 man-months. Thirty-nine scientists from 
the United States spent 20.20 man-months in visits and 
exchanges in Soviet oncologic institutes. 

NCI-Japan Society for the Promotion of Science 



During the first year of the U.S. -Japan Cooperative 
Cancer Research Program ten joint planning meetings and 
scientific symposia were held in the areas of chemical 
carcinogenesis, cancer virology, cancer immunology, 
cancer therapy, analytic epidemiology, breast cancer, 
lung cancer, bladder cancer, high-LET radiation therapy, 
cytology, and metastasis. 

Analytic Epidemiology 

In July 1974 plans were made for Japanese epidemi- 
ologists to work as exchange scientists in leading 
American laboratories and for several of them to attend 
NCI-sponsored meetings on national cancer programs to 
obtain information on cancer epidemiology. In February 
1975 discussions ensued concerning a mutual program in 



51 

approaching occupational data in respect to vaginal 
and bladder cancer and the exchange of information and 
comparison of data on the occurrence of childhood cancer 
in Japan and the incidence rates in the United States. 
In addition, special emphasis was placed on the desirabi- 
lity of developing a Japanese counterpart of the U.S. 
county maps for cancer mortality. 

Lung Cancer 

During visits to Japan, lung cancer specialists from 
the United States were able to discuss the general 
program on the treatment and control of lung cancer in 
Japan and the most recent modalities of cancer chemotherapy, 
They had an opportunity to visit research facilities and 
to assess the clinical resources available for cooperative 
programs in lung cancer. A planning meeting was held 
on lung cancer morphology staging in order to develop a 
unified system for the diagnosis and treatment of lung 
cancer. 

Breast Cancer 

In July 1974 NCI-sponsored meetings enabled a delega- 
tion of Japanese cancer specialists to observe the planning 
and current programs of the Breast Cancer Task Force, 
as well as to attend a scientific conference on estrogen 
receptors. In February 1975 five Japanese cancer special- 
ists participated in the Breast Cancer Task Force meeting 
held in San Antonio, Texas. At a special meeting, the 
Japanese group identified four areas for possible coopera- 
tion: (1) early and/or minimal breast cancer; (2) 
standardization and comparison of end results; (3) compa- 
rative epidemiology; and (4) standardization of criteria 
for evaluation of therapy. The Japanese Breast Cancer 
Working Group has been reorganizing its program to 
correspond to the organization of the NCI Breast Cancer 
Task Force. Future plans were discussed for long-range 
cooperation in these areas. 

Cancer Therapy 

A 3-day joint symposium was held on "Comparative 
Study on Cytosine Arabinoside and Cyclocytidine" and 
a workshop on the phase I study was held in Tokyo, 
February 13-15, 1975. Five American scientists and 30 
Japanese participated. Experimental and clinical studies 
indicate that the American drug, cytosine arabinoside 
(Ara-C) , is more effective than cyclocytidine (Japanese) 
in acute myelocytic leukemia and less toxic. The use 
of combination chemotherapy and combined modalities as 
well as the possibilities of cooperative phase I studies 
of new drugs were discussed. 

A cooperative study on gastrointestinal tumors is 



52 

planned for December 1975 in Japan. A symposium on the 
status of bleomycin and nitrosoureas in Japan and the 
United States and surgical adjuvant approaches will be 
proposed to be held in Hawaii, February 1976. 

Bladder Cancer 

The result of a planning meeting in Wisconsin, 
February 1975, was general agreement that the Joint 
U.S. -Japan workshop conference on "Experimental Models 
for Bladder Cancer" be held in December 1975 during which 
15-20 scientists from each country discuss and plan 
cooperative research on experimental model systems. 
In the spring of 1976, a workshop on the "Biochemical 
Aspects of Bladder Cancer" is planned in Kyoto, Japan. 
Tentative plans for meetings on pathology and treatment 
of human bladder" cancer etiology, epidemiology of bladder 
cancer, and bladder tumor-host response were made for 
1976-1978. 

Cytology 

In February 1975 five American scientists visited 
several research institutions and hospitals in Tokyo, 
Osaka, Fukuoka, and Sapporo to observe ongoing research 
in cytology, to review the state of the art of automated 
cytology in Japan, and to explore areas for future col- 
laborative research in cytology. 

It was observed that the Japanese scientists, in 
cooperation with several electronics firms, are developing 
instruments for cytology automation using automatic 
staining processes and cytologic scanners. The instruments 
measure the nucleus size and shape, nuclear-cytoplasm 
ratio, and nuclear density of the specimens. The instru- 
mental developments are similar to those in the United 
States. It was observed that more attention should be 
placed on the preparation and standardization of specimens 
for these studies. 

Long-range objectives for cooperation should focus 
on field testing and epidemiology, procedures for standard- 
izing cytologic tests at the clinical level, information 
exchanges on special techniques in cytology, investigative 
cytology directed toward clinical application of cyto- 
chemistry and immunocytology, and continued effort in the 
development of cytology automation through the exchange 
of research information, identification of individuals 
engaged in cytology research, and the exchange of scienti- 
fic personnel for information and collaborative research. 

Cancer Immunology 

The Joint Cancer Immunology Working Group held a 
3-day meeting in Hawaii, March 1975, dealing with 



53 



"Immunotherapy of Cancer and Its Fundamental Basis." 
Seventeen scientists discussed immunotherapy with BCG 
and related material, immunopotentiators other than 
BCG, immunotherapy with transfer factors or cells, immune 
evaluation, and other types of immunotherapy. 

Interest was expressed in clinical immunotherapy by 
both sides. As a result it was tentatively agreed 
that a second conference on cancer immunology be held 
focusing on the problems and current research in 
clinical use of immunotherapy. 

Cancer Virology 

The Joint Cancer Virology Working Group held a 
symposium on "Recent Advances in Tumor Virology," March 
1975, Hilo, Hawaii. The meeting, attended by 7 American 
and 7 Japanese scientists, enabled the scientists to 
familiarize themselves with ongoing research on RNA and 
DNA viruses in each country. Discussions were held on 
the exchange of experimental materials and information 
and research areas for future collaboration. Plans are 
now under way for a joint study of SV 40 mutants. A 
second meeting on cancer virology is being planned for 
spring 1976. 

Chemical Carcinogenesis 

A 3-day seminar, "Protease Inhibitors and Carcino- 
genesis," took place in Honolulu, Hawaii, March 1975. 
The seminar concentrated on the effect of a new group of 
protease-inhibiting compounds, such as leupeptin, antipain, 
and pepstatin, that exhibit an inhibiting effect on 
experimental carcinogenesis. Information was exchanged 
on the biochemical activity of these new compounds, as 
well as other enzyme inhibitors. 

The Japanese working group provided the Americans 
with generous supplies of the protease inhibitors to be 
distributed to American cancer researchers for their 
investigations . 

The chemical carcinogenesis groups have planned a 
U. S.- Japan- Australia tripartite conference on "Modified 
Cellular and Molecular Controls in Neoplasia" to be held 
in Hawaii, December 1975. This large conference is being 
sponsored by the National Science Foundation, the National 
Cancer Institute, and the Japan Society for the Promotion 
of Science (JSPS) . 

High-LET Radiation Therapy 

In July 1975 six American radiotherapists and 
radiation physicists visited several radiation biology 
and therapy centers in Japan for 7 days. Both joint 



54 

working groups discussed the various preclinical and 
clinical aspects of neutron radiation therapy and reviewed 
the availability of neutron beam therapy equipment, basic 
radiation biology, and dosimetry. The joint working 
groups, sponsored jointly by NCI and the JSPS, are now 
working on the development of clinical trial protocols 
for comparative studies. 

Exchange of Scientists 

Twenty-one JSPS-sponsored Japanese exchange scientists 
visited from 2 weeks to 6 months the National Cancer 
Institute and various American laboratories for conferences 
and definitive collaborative research with American cancer 
researchers. Five NCI-sponsored American scientists 
visited Japanese institutions for 2 weeks to observe and 
survey the development of the Automated Cytology and 
Instrumentation Program. During April and May 1975, 
an American scientist was engaged in collaborative 
research in chemical carcinogenesis at the Institute of 
Medical Science, Tokyo University. 

U.S. -Polish Peoples Republic 

Under the agreement between the United States 
and the Polish Peoples Republic for cooperation in the 
field of public health, NCI has established a working 
relation with the Institute of Oncology in Warsaw. 

In May 1975 an American exchange scientist visited 
the Maria-Sklodowska Curie Memorial Institute of 
Oncology in Warsaw and Krakow. During his stay this 
individual presented lectures on the clinical aspects of 
thyroid cancer, one of their continuing research efforts 
over the years, and consulted with Polish scientists on 
establishing a new therapeutic and research oncologic 
center in Warsaw. 

In June 1975 another American exchange scientist 
visited Poland and presented a lecture on the "Progress 
of Virological Studies in Cancer of Animals and Man" 
at the Institute of Oncology in Warsaw. Seminars in 
viral oncology and immunology were also conducted at the 
branches of the Institute of Oncology in Gliwice, 
Krakow, Wroclaw, and Poznan. 

Potential Agreements with Other 
Governments 

In June 1975 a meeting was held between the director, 
NCI, and members of his staff with Dr. P. Laudat, 
Scientific Director for the National Institute of Health 
and Medical Research (INSERM) , Republic of France . 
Reference was made to the 1974 Martinique meeting 
between Presidents Ford and Giscard d'Estaing. Dr. Laudat 



55 

summarized the interests of the two chiefs of state in 
furthering American-French cooperation in health, especial- 
ly in cancer research and cancer control activities. 
The consensus was that a formal agreement was not necessary, 
yet there was recognition of the need for expansion and 
greater participation in the existing NIH-INSERM agreement. 
Consequently, it was agreed to convene a small U.S. -French 
strategy group to establish means for effective cooperation 
that would include workshops on specific cancer problems 
and the exchange of scientists, information, and research 
materials . 

In May 1975 the NCI director and members of his staff 
met with a delegation of scientists from the Federal 
Republic of Germany (FRG) , representing the Ministry of 
Research and Technology, the Society of Radiation and 
Environmental Research (Munich) , and the Cancer Research 
Center (Heidelberg) . The purpose of the mission was to 
express the interest by the FRG in developing agreements 
for cooperation in research with specific U.S. agencies 
(in this case, NCI). The areas of research appealing to 
NCI and of particular interest to both the Ministry of 
Research and Technology and the Society for Radiation and 
Environmental Research are (1) instrumentation for early 
diagnosis, including pattern recognition and isotope 
scanning; (2) radiotherapy with high-energy particle 
emission; and (3) testing plant extracts from the Amazon 
region for clinical efficacy. 

The NCI hosted the visits of two scientific delega- 
tions from the People's Republic of China (PRC) , 
sponsored by the Committee for Scholarly Communication 
under the aegis of the National Academy of Sciences. In 
November 1974 six Chinese pharmacologists met with NCI 
staff working in drug development, cancer chemotherapy, 
and immunology. In May 1975 a delegation of biochemists 
and molecular biologists from the People's Republic of 
China were guests of the National Cancer Institute. 

A meeting of the U. S. -Egyptian Joint Working Group 
on Medical Cooperation was held in Washington, D.C., July 
1975. There was an exchange of a draft agreement for 
cooperation between the Ministry of Health of the Arab 
Republic of Egypt and the Assistant Secretary for Health, 
DHEW. The draft agreement is being considered by both 
governments in anticipation of formal joint approval. 

Collaborative Research 

In accordance with established tradition, the National 
Cancer Institute during FY 1975 has hosted visiting scien- 
tists, associates, fellows, and guest workers from 29 
countries, for collaborative cancer research projects with 
senior NCI investigators. Of these 104 visitors, 20 
came from Japan; 11 from India; 7 each from Israel, 



56 



Italy, and the United Kingdom; 5 each from Belgium, 
China (Taiwan) , France, and Germany; and the remainder 
from Argentina, Australia (2) , Canada (2) , Chile, Czecho- 
slovakia, Egypt (2), Finland, Greece (2), Hong Kong, 
Korea (2), Malaysia, The Netherlands (4), New Zealand, 
Nigeria, Norway, The Philippines, Poland (2), Spain, Sweden 
and Switzerland (3) . The scientists and their NCI hosts 
engaged in fundamental research, environmental research, 
clinical research, and cancer health services. There is 
no question of the value of such scientist-to-scientist 
interaction being the foundation for the development of 
an eventual comprehensive program of international 
cooperation in cancer research and research methodology. 

Within the purview of the five operating divisions 
of the National Cancer Institute, 26 grants and 91 
contracts were in effect during FY 1975 in foreign 
countries. 

Under the provisions of Public Law 480, the Special 
Foreign Currency Program, there are nine active cancer 
research projects in four foreign countries (India, 
Poland, Tunisia, and Yugoslavia) . The thrust of the 
Yugoslav project is directed toward the study of immuno- 
suppressive and antileukemic activity of pharmacologic 
agents. Four of the Indian projects are related to chemo- 
therapy, including the screening of indigenous herbal 
substances as potential anticancer drugs. 

To exemplify the benefit of this international 
collaboration in cancer research, we relate to cancer of 
the breast, which, at present, is one of the most frequent 
cancers affecting women in industrialized countries. 
Thus, under NCI contract the International Agency for 
Research on Cancer (IARC) in Lyon, France, has organized 
a special study of this problem in collaboration with 
the University of Iceland. This study of the whole 
population of Iceland has been initiated in an attempt to 
measure the degree of risk that relatives of breast cancer 
patients face of having breast cancer themselves. Such 
a study is intended to compare the relative importance of 
heredity and environment as risk factors in breast cancer. 

Studies on cancer of the esophagus are continuing in 
Iran, again, by the IARC under NCI contract. That this 
cancer shows wide geographic variation in incidence both 
between countries and between localized areas within a 
country such as Iran raises the possibility of identifying 
the causal factors. The detailed epidemiologic investi- 
gation in this study has been completed and the data are 
being analyzed. Preliminary results indicate a much 
higher intake of bread in the high-incidence areas than in 
the low-incidence areas where rice is the staple food. The 
use of sheep's milk and sheep's milk yogurt was common 
only in the areas of high incidence. No other foods 



57 



or vegetables showed any consistent relationship with the 
cancer. Small amounts of carcinogens- both N-nitroso 
compounds and polycyclic aromatic hydrocarbons- were 
shown to be present in the food samples collected, but 
the quantities seemed insufficient to explain the very 
marked geographic variations. The project is continuing 
with a case control study and with further chemical 
analyses of food samples for known carcinogens, including 
mycotoxins . 

Liaison with International Agencies 

Maintenance of an active association with internation- 
al cancer research organizations is vital to NCI and the 
national cancer program. The World Health Organization 
(WHO) is an organization through whose auspices the 
public health and medical professionals of more than 
140 countries exchange their knowledge and experience on 
health problems such as cancer. An integral part of 
NCI's international activities is shared with other organi- 
zations such as the International Union against Cancer 
(UICC) , the International Agency for Research on Cancer 
(IARC) , and the European Organization for Research on 
Treatment of Cancer (EORTC) . The fruits of NCI's contri- 
bution toward the support of these organizations and 
agencies are evident from the progress being made in 
the international arena where effort continues toward 
achieving the highest possible level of health throughout 
the world. 

The registration of cancer morbidity on an interna- 
tional scale is a prerequisite to studying the signifi- 
cance of geographic variations and distribution. At 
present, the IARC is collaborating with the International 
Association of Cancer Registries to collect and publish 
data under comparable conditions from different parts of 
the world. The data are stored on magnetic tape in 
the data-processing unit at WHO headquarters. The morbid- 
ity data complement the mortality statistics routinely 
collected by WHO. Since an internationally acceptable 
and standardized classification of all forms of cancer 
is essential for the systematic registration of cancer 
mortality and morbidity, IARC has been involved in prepar- 
ing the section on tumors for the next revision of the 
International Classification of Diseases (ICD) , to be 
published by WHO. Included in this revision as a voluntary 
option will be a coding scheme for the histologic classi- 
fication of tumors. This coding scheme is recognized to 
be of increasing importance in cancer registration, and 
will be especially valuable for identifying rare cancers 
which might otherwise be lost in the registration system. 

An inevitable feature of epidemiologic studies is the 
long time taken for them to reach completion and publica- 
tion. It is thus quite likely that during the period of 



58 



a given study, other workers with a similar interest may 
start collecting similar data. While duplication in 
epidemiology can provide valuable information, this will 
only be so if the methods of collecting and analyzing 
the data are comparable. It is therefore desirable to 
establish some form of clearinghouse, from where 
epidemiologists working in different countries could be 
informed of studies in progress in an effort to avoid 
unnecessary duplication and ensure that whatever dupli- 
cation is needed will lead to results that are 
comparable legitimately. Accordingly, IARC, in association 
with the German Cancer Research Center, Heidelberg, 
Federal Republic of Germany, has planned a clearinghouse 
for current epidemiologic studies and related investiga- 
tions in high-risk groups, including those subjected to 
occupational exposures to potential carcinogens. 

The coordination of studies in high-risk groups and 
those subjected to occupational exposures will also 
contribute to the work of the IARC in preparing its 
monographs on the evaluation of carcinogenic risk of 
chemicals to man. 

The IARC is actively engaged in collecting, sifting, 
and evaluating all published data relating to chemical 
carcinogenicity testing and to epidemiologic studies 
of the levels of human exposure to chemicals and, where 
available, of their carcinogenic effects on man. The 
program has resulted in the publication of IARC monographs 
on the evaluation of carcinogenic risk of chemicals to 
man. A total of 160 substances have been scrutinized and 
the results are included in the six volumes already 
published. 

The selection of substances to be included in the 
monographs conforms to two criteria. There must be evid- 
dence of carcinogenicity of the substance in experimental 
animals and evidence of human exposure to the substance. 
The highest priority has been given to assessing those 
substances for which carcinogenicity in man was suspected. 
The preparatory work of selecting chemicals and collecting 
information on them has been carried out in collaboration 
with the NCI and the Stanford Research Institute. 

Under NCI sponsorship, the Committee on International 
Collaborative Activities (CICA) of the UICC is assisting 
in the compilation of an International Directory of 
Specialized Cancer Research and Treatment Establishments, 
as a service to the international cancer research 
community. A preliminary edition was compiled for 
distribution during the International Cancer Congress in 
Florence, Italy, October 1974. This directory will be 
compiled now in a comprehensive edition and provisions 
are included for regular updating. The directory 
included information on comprehensive cancer centers, 



59 



cancer research institutes, university departments or 
biomedical research centers engaged in a structured 
program of cancer research, and hospitals or other medical 
establishments having a separate but identifiable 
organizational cancer department or unit. This project 
is an integral segment of the ICRDB program, its source 
of support. 



NATIONAL HEART AND LUNG INSTITUTE 

U.S.-U.S.S.R. Health Exchange 

Cardiovascular Portion 

The mutual interest in cardiovascular diseases stems 
from a joint concern about the major threat that these 
diseases pose to the health of mankind. Heart disease is 
a health problem of great importance to the peoples of 
many nations. It is the principal cause of death both in 
the Soviet Union and in the United States. It has exten- 
sive personal and social implications for large segments 
of the population not only in terms of unexpected deaths 
but also because it leads to chronic illness and loss of 
work capability. The solutions to these problems repre- 
sent difficult scientific challenges. Much more remains 
to be learned in order to bring these diseases under con- 
trol. Application of existing knowledge could also 
decrease illness and death from cardiovascular diseases. 
It is hoped that the U.S.-U.S.S.R. collaborative program 
will accelerate progress toward these goals. 

The U.S.-U.S.S.R. Joint Program in Cardiovascular 
Diseases, one area included in the original 5-year agree- 
ment between these governments, stresses that "the parties 
agree to direct their initial joint efforts toward com- 
bating the most widespread diseases, such as cardiovascu- 
lar... diseases, because of the major threat that they pose 
to man's health." A key element in this agreement that 
was not included in earlier cooperative programs is the 
mutual planning and execution of joint research activities 
in both countries according to an organized work plan and 
common protocols. A second important innovation is the 
provision that the mutual cooperation take place directly 
between specific U.S. and U.S.S.R. health institutions. 
Thus, the National Heart and Lung Institute of the National 
Institutes of Health was designated to collaborate with its 
counterpart institution of the Soviet Academy of Medical 
Sciences, the A. L. Myasnikov Institute of Cardiology in 
Moscow. 

The individuals responsible for organizing the ini- 
tial efforts in the joint U.S.-U.S.S.R. cardiovascular 
research programs were Dr. Theodore Cooper, now Assistant 
Secretary for Health and then Director of the National 
Heart and Lung Institute; Professor Eugene Chazov, Deputy 
Minister of Health of the Soviet Union? and Professor Igor 
Shkhvatsabaya, Director of the A. L. Myasnikov Institute 
of Cardiology. 



61 



62 



At its first meeting in 1972, the U.S.-U.S.S.R. joint 
committee selected four programs for initial collaborative 
efforts in cardiovascular diseases: pathogenesis of arte- 
riosclerosis, management of ischemic heart disease, myo- 
cardial metabolism, and congenital heart disease. Since 
the 1972 agreement, further meetings of U.S. and U.S.S.R. 
researchers have identified and agreed upon two new areas 
for joint cardiovascular research: sudden death and blood 
transfusion, blood components, and prevention of hepatitis, 
with particular reference to cardiovascular surgery. In 
addition, an artificial heart research and development 
program is being developed under a separate agreement 
signed June 28, 1974, in Moscow. 

1. Pathogenesis of Atherosclerosis 

Arteriosclerosis, the most common cause of cardio- 
vascular disease, is directly or indirectly responsible 
for more deaths in the United States and the Soviet Union 
than any other disease. Because hyperlipidemia is strongly 
suspected to be a major risk factor in causing premature 
atherosclerosis and subsequent ischemic heart disease, 
this subject area was chosen for joint study. Quantita- 
tively, hyperlipidemia is perhaps the most important of 
the known risk factors for arteriosclerosis. Not only is 
extreme hyperlipidemia associated with high risk, but even 
the "average" values believed to be present in American 
and Soviet populations are associated with higher risks 
than are the average levels in populations of several 
other countries. 

Automated techniques for classifying hyperlipidemia 
according to standardized methods have been set up in a 
number of lipid research clinics (LRC) in the United States 
and Canada, supported by the National Heart and Lung In- 
stitute. The major task of the current network of 12 lipid 
research clinics is to collect data on the prevalence of 
arteriosclerosis and information concerning environmental, 
familial, and genetic influences. It is expected that new 
standards of "normal" for lipids and lipoproteins for Amer- 
ican populations will be set by this study. In addition, 
an intervention trial is under way in the United States to 
determine the beneficial effects of treatment of hyperli- 
pidemia. 

Through the U.S.-U.S.S.R. agreement this continentwide 
study has been expanded to encompass an extensive compar- 
ison of the nature and magnitude of the arteriosclerosis 
problem in the United States and in the Soviet Union. 
Combining the data from the U.S. clinics and the recently 
established U.S.S.R. clinics will significantly broaden 
the inferences and conclusions that can be drawn from the 
study . 



63 



The U.S. -U.S.S.R. study which involves large numbers 
of individuals (men, 40-59 years old) in the two countries 
who are being studied according to carefully developed 
common research protocols, intends to compare the preva- 
lence of hyperlipidemia and ischemic heart disease in the 
United States and the U.S.S.R. In the United States the 
lipid research clinics program expects to study approx- 
imately 22,000 individuals in the initial phase (phase 1) 
of the study; and from 3,000 to 5,000 in the second, more 
specialized, phase of the study (phase 2). In the U.S.S.R., 
the study is being conducted in Moscow and Leningrad. 
10,000 individuals will be studied in phase 1 and 
approximately 2,500 in phase 2. 

This program has been the most active program in the 
cardiovascular portion of the U.S. -U.S.S.R. health agree- 
ment since its beginning. From the time of the signing 
of the agreement on these studies, collaboration in this 
area has been directed toward the achievement of standardi- 
zation and unification of epidemiological and biochemical 
methodology. During the past year significant progress 
was made toward achieving these goals. In July 1974 a U.S. 
delegation visited the Soviet Union to review the progress 
in the cooperative study and the pretrials that had just 
been completed in the clinics in Moscow and Leningrad and 
to resolve any difficulties that may have arisen since the 
last joint meeting. The delegation included five members 
of the joint U. S. -U. S ,S .R. steering committee and five 
members of the working group. 

General issues on which agreement was reached included 
a specific timetable with deadlines for each sequential 
step leading to the formal study. U.S.S.R. representation 
at meetings of the LRC directors and the U.S. Prevalence 
Subcommittee was agreed to be desirable. Provisions were 
made to improve the communications network and to transmit 
data via telex until the Soviet computer system can be 
developed and made operational. To institute regular 
contact, it was agreed to exchange monthly reports. 

In the biochemistry area, laboratory standardization 
and quality control procedures were reviewed and clarified 
where necessary. Tests for determining secondary causes 
of hyperlipoproteinemia were discussed, and it was agreed 
that each clinic would conduct its own tests, using 
identical methodology, reagents, and standards. A certain 
number of split samples would be exchanged by the two 
laboratories to maintain comparability. In addition, the 
Center for Disease Control, Atlanta, will provide quality 
control pools and primary standards for secondary tests. 

The epidemiology working group reviewed and defined 
U.S.S.R. procedures for selecting the population sample. 
In addition, significant discrepancies between the U.S. 



64 



and U.S.S.R. forms were discussed and amended. Plans 
were made to initiate and test the exchange of study data. 

Training and certification procedures for U.S.S.R. 
dietitians were formalized. Four dietitians were cer- 
tified during the visit. Agreement was reached on quality 
control procedures for monitoring the coding of nutritional 
data. 

In the cardiology area, it was agreed that the U.S.S.R. 
clinics would conduct the graded exercise test using the 
treadmill. This will ensure comparability of cardiological 
data. Agreement was also reached on the procedures for 
conducting resting and stress ECG tests and for coding 
ECG recordings. 

Two Soviet scientists visited the United States in 
November 1974 to attend the meetings of the Arterio- 
sclerosis Council of the American Heart Association and 
to represent the Soviet lipid research clinics at the 
fall 1974 meeting of the U.S. lipid research clinic 
directors in Dallas, Texas. Key items of the study were 
discussed in biochemistry, nutrition, epidemiology, and 
cardiology. A number of lingering problems in each area 
were reviewed. 

A U.S. working group visited the U.S.S.R. in March 
1975 to finalize preparation for the formal U.S.S.R. 
prevalence studies. At the time of the visit, the 
Leningrad LRC was completing its pilot study, having 
successfully passed laboratory standardization in January. 
During the visit, the working group reviewed preliminary 
pilot data from Leningrad and visit 1 screening procedures 
at both clinics. It was confirmed that the Moscow lab- 
oratory had passed the standardization program. 

Training and certification of all interviewers is now 
complete. ECG certification forms and tapes have been 
completed in both clinics. The principal milestones in 
the two Soviet lipid research clinics since the March 
visit include (1) completion of pilot studies in both 
clinics, (2) initiation of visit 1 of formal study, and 
(3) initiation of visit 2 of formal study. 

Two senior U.S.S.R. scientific workers visited the 
United States in 1975 for 2 months. Their visits included 
work at the laboratories of the Molecular Diseases Branch, 
NHLI , and the Center for Disease Control. They also 
attended the lipid research clinics directors' meetings in 
Bethesda, as well as the meetings of the American Society 
for Clinical Investigators in Atlantic City. 



65 



2. Management of Ischemic Heart Disease 

While problem area 1 deals with the very important 
subject of defining ischemic heart disease and its assoc- 
iation with environmental and inherited factors in that 
large portion of the populations in both countries who 
are at risk of developing heart disease, problem area 2 
is concerned with a second large segment of the- populations 
in the U.S., U.S.S.R., and worldwide who are already 
victims of the disease. This research is patient-oriented 
and seeks to find ways to minimize mortality, morbidity, 
and suffering. 

In the United States, the surgical technique under 
study uses a blood vessel graft to bypass a narrowed or 
occluded segment of a coronary artery. Although over 
25,000 such operations are done annually in the United 
States for treating chronic disability from angina pec- 
toris and heart attacks, the indications for and the 
effects of coronary artery surgery in the treatment of 
coronary heart disease remain to be determined. While 
coronary artery surgery is very popular in the United 
States, this method has received little following in 
similar patient populations in the U.S.S.R. Conversely, 
some of the medical approaches in the U.S.S.R. are un- 
familiar to U.S. heart specialists. 

Through the U.S. -U.S.S.R. agreement a collaborative 
study is being developed that takes advantage of this 
unique opportunity to systematically assess and compare 
the way well-defined heart disease patients are treated in 
the two countries. The ultimate goal of this coordinated 
study is to assess various medical versus surgical ther- 
apies for the treatment of ischemic heart disease. These 
therapies include "differential" intensive medical manage- 
ment in the U.S.S.R., "conventional" standardized medical 
management in both countries, and coronary bypass surgery 
in the United States. 

Between 1972 and 1973, initial agreement was reached 
on methodological bases of the U.S. -U.S.S.R. joint study, 
such as the criteria for patient selection, patient ex- 
amination, therapy, and assessing the effectiveness of 
treatment. Pilot studies have been completed both in the 
United States and the Soviet Union. Since then, U.S. and 
U.S.S.R. cardiologists and cardiovascular surgeons have 
met repeatedly to further define criteria for the selection 
of patients who will receive differential medical treatment 
and to develop specific work plans for the various phases 
of the joint study. An exchange of fellows also took 
place in 1973 and 1974. 



66 



Well-defined patients, that is, patients who both the 
American and Soviet physicians are in complete agreement 
concerning the state of their coronary artery diseases, 
will be placed in one of three groups. Two "intensively 
treated" groups and one "reference" group, will be com- 
posed of men, 30 to 60 years of age. 

In the United States, patients who have one or more 
coronary arteries occluded by lesions causing greater 
than 70 percent obstruction will be treated surgically. 
In the Soviet Union, the method of treatment for patients 
with identical heart disease will be entirely nonsurgical. 
It will consist of a combined drug therapy and exercise 
program carried on in the hospital and, after discharge, 
in a health resort. 

It is anticipated that the end points for the joint 
study will occur in 5-8 years. Two years are required 
for patient intake. A subsequent 5 year follow-up period 
plus 1 year for data analysis is anticipated. During the 
5-year follow-up period the patients in the U.S . -U.S.S.R. 
international study will be examined periodically to 
evaluate the effectiveness of their respective therapies. 

From May 26 to June 7, 1974, a U.S. delegation visited 
the U.S.S.R. to review the progress and to develop 
further plans for the upcoming year. The overall study 
design and the protocol of February 1973 were reviewed 
in detail. Specific task forces also met on angiography 
and electrocardiography. Although modifications in the 
detailed protocol were largely clarifications, some 
specific modifications - such as the elimination of the 
requirement for a specific number of anginal attacks per 
week, angiographic and ventriculographic characterization 
of patients in the intensively managed group, elimination 
of the requirement that the conventional medical management 
include only the intermittent use of such agents as long- 
acting nitrates and propranolol, and a decrease in the 
frequency of required follow-up - were advanced. A mem- 
orandum of understanding was drawn up, detailing the 
future plans of collaboration. 

A reciprocal visit by a Soviet delegation to the United 
States, October 25 through November 7, 1974, enabled 
scientists to review experiences in the pilot studies in 
the Soviet Union and in the United States, to further 
clarify plans and protocols, and to develop plans for the 
future. Based on experiences of the domestic studies in 
each of the two countries and the international U.S.-U.S.S.l 
plans, all of which were in advance development stages, 
opportunities for improvements in each of these plans 
became evident. In addition, record forms were exchanged 
that will serve not only to develop the international 
U.S. -U.S.S.R. study, but to aid each of the two domestic 



67 



studies in their future development. Particular attention 
was paid to the analysis of coronary angiograms, review of 
electrocardiograms, and patient follow-up. 

Since the October 1974 joint meeting, communication 
has been maintained between the U.S.-U.S.S.R. coordinators 
in order to complete collaborative plans in a timely 
fashion. In May 197 5 the U.S. coordinator forwarded 
information to the U.S.S.R. on the pilot phase of the U.S. 
studies, as well as an extensive document containing the 
plans for the definitive U.S. study. These plans had just 
been reviewed by a U.S. advisory group at that time and 
formally approved by the National Heart and Lung Institute. 

In preparation for the September 21 - October 3, 1975, 
U.S.S.R. visit by a U.S. delegation, the United States 
has prepared copies of angiograms for joint viewing to 
further U.S. and U.S.S.R. standardization of angiographic 
interpretation. Also, a computer program that will print 
out the data from the domestic U.S. study in the sequence 
of the U.S.-U.S.S.R. international study is being developed. 
It is expected that results of this effort will be available 
for the September meeting. 

3. Myocardial Metabolism 

A fundamental understanding of the structure and 
function of the heart muscle is crucial to the development 
of improved methods of prevention and therapy for heart 
disease. Specifically, it is important to search for 
therapies that will enable the heart muscle to survive 
a heart attack and to develop methods that may prevent 
additional heart muscle damage. 

The role that this research project will play in 
future cardiovascular programs is likely to be a very 
important one, both in terms of joint development of new 
therapies and methods of prevention. Research areas 
currently being addressed by Soviet and American scientists 
include the manner in which heart muscle cells obtain 
energy, regulate their growth, coordinate their contrac- 
tions, and respond to induced alterations in their envir- 
onment. These studies entail basic exploration at the 
most sophisticated levels of modern medical science, in- 
cluding physiology, molecular biology, biochemistry, and 
biophysics . 

Because of this inherent complexity and specialization, 
it is difficult to identify areas where major collaborative 
research projects can be carried out in the immediate 
future. However, the regular and constant reporting of 
research results and the exchange of technical information 



68 



can be of invaluable assistance to researchers in the 
United States and the U.S.S.R. in their common goal to 
prevent and control heart disease. To accelerate this 
exchange of information, under the joint exchange agree- 
ment, a symposium was held in the United States in 
November 1973. Extensive discussion of many different 
research projects relating to myocardial metabolism led 
to the identification of new leads and ideas that will 
serve as the basis for future collaborative efforts. 
Significant advances in the understanding of myocardial 
metabolism were identified, which demonstrated the high 
level at which this research is conducted both in the 
United States and the Soviet Union. 

The proceedings of the symposium have been published 
in English as a supplement of the journal Circulation 
Research . The proceedings have also been published in 
Russian in the Soviet Union. Arrangements have been 
made for the regular exchange of important research reports 
for mutual publication on a regular basis. Professor 
Chazov's book, Myocardial Infarction , has been translated 
into English under the auspices of the National Library 
of Medicine and the National Heart and Lung Institute and 
will be published in the United States in the near future. 

Three U.S. exchange fellows spent extended periods of 
time working in Soviet laboratories in the area of myo- 
cardial metabolism. Dr. Rannels and Dr. Shell worked 
mainly in the myocardial research laboratories at the 
Myasnikov Institute of Cardiology in Moscow, but visited 
cardiovascular institutes in other Soviet cities as well. 

In the spring of 1975, Dr. Muller from the Department 
of Medicine, Harvard Medical School, spent 3 months in the 
U.S.S.R. His project was an intensive joint U.S.-U.S.S .R. 
clinical study of the effect of hyaluronidase on reducing 
infarct size in man. Although complete analysis of the 
data of this study has not been made, preliminary analysis 
appears to support the hypothesis that hyaluronidase treat- 
ment reduces infarct size. 

Dr. Saks, senior scientific worker at the Myasnikov 
Institute of Cardiology, visited the United States as a 
Soviet fellow in the spring of 1975. His program included 
visits to the Laboratory of Cell Biology, National Heart 
and Lung Institute; the Johnson Research Foundation at 
the University of Pennsylvania in Philadelphia; the 
Milton S. Hershey Medical Center, Pennsylvania State Uni- 
versity; Johns Hopkins School of Medicine; the Cardio- 
vascular Research Laboratory, UCLA Medical Center in Los 
Angeles; and the Department of Physiology, University of 
California at Berkeley. In addition he attended several 
scientific meetings. Dr. Saks, and one of the U.S. 
exchange fellows, Dr. Shell, have completed a research 



69 



paper as a result of their collaborative research in Moscow; 
the paper, "Studies of Mechanisms of Energy Transport in 
Heart Cells", will be published in Circulation Research 
in 1975. 

In June 1975 a second Joint Symposium on Myocardial 
Metabolism was held in the Soviet Union to promote further 
exchange of the latest information in this important 
area of research. During the joint discussions in 
Sochi, both sides agreed that as a result of the U.S.- 
U.S.S.R. collaborative efforts initiated following the 
1973 U. S.-U.S. S.R. symposium in Ponte Vedra, particularly 
the exchange of young scientists from both countries, 
important new lines of joint research have been outlined 
of potential benefit to the people of the United States 
and of the Soviet Union. The following studies were 
completed or are in progress: clinical studies aimed at 
limiting the extent of damage to heart muscle following 
myocardial infarction, studies of the regulation of protein 
synthesis and degradation in the myocardium, studies of 
energy transport in the myocardium, and properties of 
creatine phosphokinase from heart muscle. 

The topics discussed included disturbance in the 
function of the heart muscle in patients with ischemic 
heart disease, the effect of hormones and drugs on normal 
and ischemic heart muscle, changes in the blood circulation 
to the heart during ischemia, energy processes in the heart 
muscle, and possible clinical applications of the results 
of these basic studies. The proceedings of the symposium 
will be published in Russian in the Soviet Union and in 
English in the United States. 

4. Congenital Heart Disease 

Congenital heart disease is an important disease of 
children and young adults, both in the United States and 
in the Soviet Union. In the United States, about eight 
of every 1,000 children are born with this disease. 

There are many types of congenital heart defects. 
Each may occur alone, or in combination. Less than 3 
percent are known to be related to a particular event or 
disorder occurring during pregnancy, such as rubella 
infection, or the use of certain drugs. Thus, in the great 
majority of cases congenital heart disease cannot as yet 
be prevented and, therefore, the only hope for these 
children is therapeutic measures to correct or control 
their heart disease. 

Congenital heart disease may cause considerable im- 
pairment of the quality of life of the patient surviving 



70 



into adulthood. Fortunately, approximately 80 percent of 
infants with this disease can now be cured or helped with 
corrective surgery. These surgical successes are now being 
expanded by the development of diagnostic and surgical 
techniques applicable to the newborn. 

The objectives of the U.S . -U.S .S .R. collaboration in 
this research area are to explore new methods of diagnosis 
and postoperative care in order to further reduce mortality 
from congenital heart disease and to improve the surgical 
treatment of complex heart defects. It is hoped that 
through the exchange of information in this problem area, 
Soviet and American surgeons will be able to achieve a 
higher rate of success in corrective surgery of congenital 
heart defects. The proceedings of the second joint sym- 
posium will be published by the Soviets in both English 
and in Russian. It is expected to be published in the 
first quarter of 1976. The United States was responsible 
for the editorial review of the English version of the 
proceedings. The proceedings will be distributed to 
the U.S. and U.S.S.R. participants and all interested 
scientists . 

5. Sudden Death 

Fifty percent of all deaths from coronary heart 
disease occur suddenly. Sudden death coronary arterio- 
sclerosis may occur in individuals with no symptoms of 
heart disease, in patients with angina pectoris, in 
patients with a history of heart attacks, and during an 
acute heart attack. The immediate mechanism of sudden 
death is believed to be a disturbance in the rhythm of 
the heart. 

The topic of sudden cardiac death is of major concern 
to scientists in the United States. A series of studies 
have been undertaken to identify factors that precipitate, 
or "trigger", acute heart attacks in patients with coronary 
arteriosclerosis. It is hoped that these studies will 
help to elucidate factors in the person or his environment 
that make him highly susceptible to potentially lethal 
heart attacks and to discover premonitory signs and sym- 
toms that may warn the patient or his physician of an 
impending attack in time to take preventive measures or 
to hospitalize the patient before the onset. Other studies 
have involved the identification of factors that cause or 
contribute to a quickly fatal outcome after onset and the 
development of practical methods for treatment of the 
very early stages of the acute heart attack in an effort 
to lessen the risk of sudden death. 

The avoidance of sudden death from cardiac arrhythmia 
is a very important area of study for any collaborative 



71 



efforts to reduce coronary heart disease mortality. Soviet 
and American physicians alike are looking for effective 
ways to deal with the problem. 

The area of sudden death was one of the new cardio- 
vascular program areas approved under the official agree- 
ment at the annual meeting of the Joint U.S .-U.S .S.R. 
Committee for Health Cooperation in 1973. A. U.S. dele- 
gation visited the Soviet Union in the fall of 1973 to 
discuss the development of initial plans for collaboration 
in this area. Soviet and American scientists exchanged 
information and held extensive discussions on the follow- 
ing topics: the magnitude of the sudden death problem in 
both countries, risk factors for sudden death, the rela- 
tionship between arrhythmias and sudden death, current 
approaches to management of sudden death in the United 
States and the Soviet Union, emergency treatment that 
might be useful in controlling arrhythmias, suggestions 
for joint U.S .-U.S .S .R. projects, and the development of 
mechanisms for ongoing exchange. 

In contrast to problem areas 1 and 2 , at the initia- 
tion of this area of collaboration, there were no current 
or projected large-scale collaborative activities in 
either the United States or the Soviet Union. A number 
of pilot studies were in progress in the United States. 
The immediate task of both the United States and the 
Soviet Union was to rapidly assess the current state of 
the art and to form interested and competent working groups 
to explore current activities and future opportunities 
for joint research in sudden death. 

U.S. scientists interested in and working in the area 
of sudden death met in the fall to exchange current infor- 
mation on the relationship between arrhythmias of the 
heart and sudden death. The proceedings of this meeting 
will be published shortly and will be made available to 
the Soviet scientists in problem area 5. Also in the 
fall of 1974 the National Heart and Lung Institute, in 
collaboration with the Division of Computer Research and 
Technology, sponsored a conference on computers in cardi- 
ology. The topics discussed during this conference have 
direct relevance to this problem area, and the proceedings 
of the conference have been forwarded to the Soviet 
scientists engaged in the U.S .-U.S .S .R. collaborative 
activities in sudden death. 

To move ahead in this area, the United States has 
provided U.S. S.R. scientists with monitoring equipment 
for the joint study. Shortly after the third joint 
committee meeting, the U.S. S.R. reported that four Soviet 
physicians had already been trained to operate the equip- 
ment. However, Professor Lukomsky ' s untimely death post- 



72 



poned any possible expansion of collaborative activities, 
and the U.S.S.R. has requested a delay in initiating the 
collaborative effort. In January 1975, the Soviets 
reported having difficulty with the monitoring equipment 
provided by the United States and requested U.S. assis- 
tance in analyzing the problem. A series of magnetic 
tapes were forwarded to the U.S. coordinator for analysis. 

A U.S. delegation visited the U.S.S.R. in June 1975 
to review program plans and to develop a plan for the 
upcoming U.S. visit by a Soviet delegation. The major 
discussions of activities in this problem area were held 
at the Myasnikov Institute of Cardiology. The delegation 
also visited the Institute of Cardiology in Tbilisi. The 
Soviets have made a definite new commitment in the area 
of joint work on sudden cardiac death. A decision has 
been made to expand joint collaboration with the Myasnikov 
Institute to involve cardiology institutes in Kaunas, 
Lithuania, and Tbilisi, Georgia, thus moving the collab- 
oration toward a truly national Soviet effort in this 
problem area. 

The U.S. coordinator presented an overview of sudden 
cardiac death studies in the United States. Like the 
United States, the U.S.S.R. is also pursuing two main 
directions of research in sudden death: basic studies 
of sudden death and public health programs aimed at 
identifying the population at risk. 

Some of the most recent work in the area of sudden 
cardiac death in the United States has been detailed, 
such as determination of the prevalence of ectopic activity 
in the population and qualitative and quantitative rela- 
tionship of this ectopic activity to the major risk factors 
being studied in the multiple risk factor intervention 
trial population. 

During its visit, the U.S. delegation was informed 
by the U.S.S.R. scientists that there had been considerable 
delay in initiating the joint studies with the monitoring 
equipment provided by the U.S. Apparently, the Myasnikov 
Institute where the studies were to have been performed 
had been closed for about a year. It was only in January 
1975 that the 24-hour monitoring study could be started. 
The current studies are on patients who have had a myo- 
cardial infarction, conducted in accordance with the pro- 
tocol previously agreed upon in joint discussions with the 
United States. The purpose of task 1 is to determine the 
prevalence of arrhythmias in patients and the relationship 
to sudden death. This task is being implemented. Task 2 
on the U.S.S.R. side will be concerned with the epidemio- 
logy of sudden death. It will be conducted in healthy 
people, in people with risk factors, and in people with 



73 



ischemic heart disease. The purpose of task 2 is to 
determine the correlation and identify specific conditions 
for increased trends of sudden death. U.S. monitors 
and analyzers will be used only for task 1. 

The current plan for U.S.S.R. task 1 is for the 
Myasnikov Institute to monitor 400 patients a year for 
3 years and for the cardiology institutes in Tbilisi and 
Kaunas to monitor 100 patients a year each. These patients 
will also be monitored for 3 years. 

The U.S. coordinator met with the Myasnikov staff 
directly involved in the monitoring study to review 
accumulated data. He also reviewed in detail the U.S.S.R. 
magnetic tapes submitted to the U.S. for analysis. Detailed 
reports were left with the Soviet scientists for their 
study and comparison. 

The U.S.S.R. is continuing the study of the relation 
of ventricular ectopic activity to risk of sudden death 
in patients with ischemic heart disease, using the equip- 
ment provided by the U.S. for monitoring and analyzing 
the data. U.S. scientists have agreed to provide technical 
consultation as needed. 

U.S.S.R. and U.S. scientists are also proceeding as 
planned with studies of frequency of different types of 
ventricular ectopic activity in selected high-risk pop- 
ulations and in the general population and have agreed 
to exchange results from these studies. 

6. Blood Transfusions, Blood Components, and the 

Prevention of Hepatitis in Cardiovascular Surgery 

The past two decades have witnessed rapid advances 
in the use of blood for therapeutic purposes. High-quality 
blood and blood products are essential for the effective 
treatment of many diseases. To give the patient enough 
of what he needs and when he needs it requires recruiting 
donors, collecting the blood, separating it into its 
components, detecting and eliminating disease-causing 
agents, matching the components for compatability , and 
administering the blood to the patient in a failsafe manner. 

The problem of blood transfusion, blood components 
and prevention of hepatitis, with particular reference to 
cardiovascular surgery, was approved as a new problem area 
in 1973, at the joint U.S .-U.S.S .R. committee meeting. 
The problem area not only provides a link between our two 
countries in an area of mutual interest and needs, but it 
also promotes the collaboration of internists and surgeons 
who may view the problems of blood management from dif- 
ferent perspectives. 



74 



A U.S. delegation made a preliminary visit to the 
U.S.S.R. in December 1973; a reciprocal visit by a Soviet 
delegation was made to the U.S. in October 1974. The 
U.S.S.R. delegation visited many important blood centers 
and laboratories in the United States: The New York 
Blood Center, the International Hemophilia Training Center 
at Mt. Sinai Hospital in New York, the Ortho Diagnostics' 
research laboratories and production facilities in Raritan, 
the NIH Clinical Center Blood Bank, laboratories at the 
Bureau of Biologies of the Food and Drug Administration, 
and the American Red Cross. 

The second joint U. S. -U. S . S . R. working meeting in 
this problem area was held at the National Institutes of 
Health, October 21-23, 1974. 

The delegation adopted two major themes for colla- 
borative scientific investigations: approaches to the 
prevention of hepatitis in blood transfusion, particularly 
in cardiovascular surgery and the use of whole blood, 
blood components, blood derivatives, and blood and plasma 
substitutes with particular emphasis on cardiovascular 
surgery. 

To approach this collaborative effort in a well- 
organized manner, the U.S. and U.S.S.R. coordinators 
exchanged in January 1975 lists of principal centers in 
each country engaged in research in the identified subject 
areas. In March 1975 the coordinators exchanged preliminary 
plans for implementing projects in the two major themes. 
Discussions of these preliminary plans will be held during 
the September 1975 U.S.S.R. visit of a U.S. delegation. 
The key element in the development of these joint projects 
is the exchange of young health specialists who will 
actively participate in evolving the program. It is 
anticipated that the first exchange of U.S. and U.S.S.R. 
health specialists in this area will begin at the end 
of 1975 or early 1976. 

Artificial Heart Research and Development 

In June 1974 after 2 years of exploratory discussions 
and exchanges, the governments of the U.S. and the U.S.S.R. 
signed an agreement designating the field of artificial 
heart research as a new area of cooperation. The U.S.- 
U.S.S.R. agreement in artificial heart research and 
development provides for joint efforts in research on, 
and the development and testing of devices, materials, 
instruments, and control mechanisms that will provide 
cardiovascular support, including total heart replacement. 



75 

Present and foreseeable techniques of general and 
pharmacologic management of acute and chronic heart 
failure or shock still leave a substantial fraction of 
patients with compromised or fatally impaired heart 
function. By supportive mechanical devices, it is possible 
to assume some of the pumping function of the heart and 
to relieve its work load. At present, such techniques 
are applicable for brief periods in man and have been 
employed for longer periods in experimental animals. 
For example, recent studies of patients in the United 
States have shown a definite reduction in the amount of 
heart muscle damaged from heart attack when the heart 
is assisted during recovery by means of a device called 
the intraaortic balloon. 

Partial and totally implantable heart assist devices 
may be of significant use in the future for the correction 
of acute and chronic heart failure. In recent studies 
in the United States a device to assist the left side of 
the heart has performed successfully in experimental 
animals. Mechanical techniques for augmenting or sub- 
stituting for the performance of the heart must be expanded 
to encompass emergency temporary devices for short-term 
management, extracorporeal assist pumps for intermediate 
periods of use, long-term implanted heart assist devices, 
and total artificial hearts. 

Related opportunities and needs exist both to explore 
the function of assisted circulation and to develop and 
improve various components of circulatory support systems. 
These components include compatible biomaterials , pumps, 
actuators, energy transforming devices, implantable 
energy systems, transcutaneous energy transmitters, and 
control systems for the devices. 

A U.S.S.R. delegation, headed by the U.S.S.R. 
Minister of Health, Boris Petrovsky, visited the U.S. in 
October 1974 to develop plans for implementing this 
intergovernmental agreement. The major collaboration 
efforts agreed upon in the October memorandum of under- 
standing were familiarization and exchange of technical 
aids and devices from each side; the holding of a joint 
conference in 1975; and preparation for a future exchange 
of samples of artificial heart devices, circulatory assist 
devices, and their subcomponents. 



Early in 1975, names of key U.S. and U.S.S.R. insti- 
tutes planning to participate in this exchange were 
telexed by each side. In April a Soviet delegation visitec 
the U.S. to further develop collaborative efforts 
initiated in October 1974, In addition, the U.S.S.R. 
delegation had an opportunity to attend the annual meeting 
of the American Society for Artificial Internal Organs, \ 



76 



participate in the ASAIO international workshop on arti- 
ficial internal organs, and visit several U.S. scientific 
institutes specializing in the development of circulatory 
assist devices and the total artificial heart. 

A joint U.S.-U.S.S.R. meeting was held on April 28 
and 29, 1975, to develop a new memorandum of understanding 
under this agreement. The major items discussed were 
scientists to participate in the program; exchange of 
these scientists, equipment, and joint protocols; inclu- 
sion in program of joint research and development of 
circulatory assistance; exchange of lists of devices 
and technical aids related to artificial heart and cir- 
culatory devices; and joint publication of results of 
studies and evaluation. 

Fellowships, Contracts, Grants 

During FY 1975, the National Heart and Lung Institute 
funded six foreign fellowships, eight foreign contracts, 
and ten foreign research grants. In addition, NHLI 
supported seven research grants with foreign affiliations. 

International Meetings and Visitors 

All divisions of the National Heart and Lung Insti- 
tute (NHLI) have sent personnel to numerous international 
scientific meetings. NHLI staff members have actively 
participated in these meetings by presenting papers, being 
discussion panelists, or representing the NHLI at the 
meetings. A brief description of some of the meetings 
follows. 

Division of Heart and Vascular Diseases 

During FY 1975, a majority of the division's pro- 
fessional staff participated in international meetings, 
among which were the Meeting of the American Society for 
Pharmacology and Experimental Therapeutics held in 
Montreal, Canada; the Fifth International Symposium on 
Drugs Affecting Lipid Metabolism, Milan, Italy; the 
Canadian Cardiovascular Society Meeting in Vancouver, 
Canada; the International Symposium on Lipids and Heart 
Disease, Stockholm, Sweden; the First International Congress 
on Twin Studies in Rome, Italy; Symposium on Hyper lipidemia 
and Coronary Artery Disease, Tel Aviv, Israel; and the 
WHO Meeting on the Effectiveness of Treatment in Mild Forms 
of Hypertension, Madrid, Spain. 

Division of Lung Diseases 

The staff of the lung division was actively involved 
in many international meetings in FY 1975. These included 



77 



the International Congress of Physiology and Satellite 
Symposium held in New Delhi, India; the WHO Workshop on. 
Epidemiology of Nonspecific Respiratory Diseases in Geneva, 
Switzerland; the International Conference on Lung Disease 
sponsored by both the American and Canadian Thoracic 
Societies and held in Montreal, Canada; and the Inter- 
national Conference on Membrane Lung Technology and Pro- 
longed Extracorporeal Perfusion in Copenhagen, Denmark. 

Division of Blood Diseases and Resources 

Examples of international meetings attended by staff 
members in this division during FY 1975 include the 
Twenty-Fifth Congress of International Society of Hema- 
tology, Jerusalem, Israel; Symposium on Fibrinolysis 
held in Montreal, Canada; and the International Committee 
on Thrombosis and Haemostasis in Basel, Switzerland. 

Division of Extramural Affairs 

The Director of the Division of Extramural Affairs 
attended the Twelfth International Congress on Diseases 
of the Chest held in London, England. 

Division of Intramural Research 

The staff of the Division of Intramural Research was 
very active in international scientific meetings during 
FY 1975. Many staff members attended more than one inter- 
national meeting to discuss their own research findings 
and to learn about research by scientists in other coun- 
tries. Examples of some of the many meetings attended by 
the DIR staff include the Second International Conference 
on Cyclic AMP, Vancouver, Canada; symposium in honor of 
Dr. Fritz Lipmann held in West Berlin, Germany; the second 
International Workshop on the Human Gene Map in Amsterdam, 
Netherlands; the Second Congress of Immunology, Brighton, 
England; the Fifth Parathyroid Conference, Oxford, England; 
the Laurentian Hormone Conference held in Mt. Tremblant, 
Canada; the Pan American Symposium on Vasoactive Peptides 
and Hypertension, Mendoza, Argentina; the Twenty-Fifth 
Congress of the International Society of Hematology held 
in Jerusalem, Israel; the Seventh World Congress of Car- 
diology, Buenos Aires, Argentina; the Fourth International 
Congress on Hormonal Steroids, Mexico City, Mexico; the 
International Congress of Lipid Biochemistry held in Milan, 
Italy; the Fifth International Symposium on Olfaction and 
Taste, Melbourne, Australia; the South American Congress 
on Pharmacology, Lima, Peru; the Fourth Workshop on Ex- 
perimental Liver Injury on Pathogenesis and Mechanisms of 
Liver Cell Necrosis, Freiburg, Germany; and the Inter- 
national Congress of Nephrology held in Florence, Italy. 



78 



General 

In addition, the institute has had representatives 
at the following meetings dealing with international 
research: Conference between the Royal Society of Medicine 
of England and the Fogarty International Center (FIC) of 
NIH to discuss proposals for future Anglo-American con- 
ferences; Meeting of the Honorary Board of Trustees of 
the Miguel Servet Fund of Spain; FIC's Conference on 
International Health Costs and Expenditures at NIH; and 
the International Conference on Women in Health. 

During FY 1975 there were numerous international 
visitors to the National Heart and Lung Institute. Some 
of these visiting foreign scientists included the U.S.S.R. 
Minister of Health, Boris Petrovsky; Dr. Katsumi Meguro, 
Deputy Chief, Medical Affairs Division, Ministry of Health 
and Welfare, Japan; Dr. Z. Pisa, Chief, Cardiovascular 
Diseases, World Health Organization, Geneva, Switzerland; 
and Dr. Lie, Chief of Cardiology at the General Hospital 
in Jakarta, Indonesia. Also, NHLI staff discussed the 
institute's programs with a number of visiting foreign 
scientific writers. 

Proposals For Future 
International Programs 

Proposals for future collaborative health research 
with Brazil, Germany, India, and Poland were submitted 
to the Fogarty International Center (FIC) in FY 1973 for 
consideration. Action on three of these proposals is 
still pending. 

During FY 1974 the National Heart and Lung Institute 
responded to inquiries from FIC concerning possible U.S.- 
Argentina collaboration in the cardiovascular area. 

In FY 1975, several discussions were held between the 
staff of the National Heart and Lung Institute and rep- 
resentatives of the Federal Republic of Germany (FRG) to 
consider proposals for collaboration between U.S. and FRG 
scientists. A summary of discussion between these two 
countries was developed jointly and formally signed. A 
workshop on artificial circulatory support, with particular 
emphasis on the area of biomaterials development, testing, 
evaluation, and the use of biomaterials in circulatory 
devices will take place in FRG in FY 1976 and will be 
attended by three American experts. At the conclusion 
of this workshop, future plans for collaboration in the 
field of artificial circulatory support will be discussed. 



NATIONAL INSTITUTE 

OF 

ALLERGY AND INFECTIOUS DISEASES 



The mission-related diseases of the National Institute 
of Allergy and Infectious Diseases (NIAID) include many 
that constitute insignificant health problems in the United 
States but have a large impact on the socioeconomic and 
health status of populations of many countries of the 
world. The international benefits of the NIAID research 
programs are of two categories: studies conducted in U.S. 
laboratories on diseases of importance mainly to other 
countries and studies conducted abroad that are either 
funded by the institute or carried out in collaboration 
with U.S. scientists. 

In addition to the ubiquitous maladies, such as 
hepatitis, tuberculosis, and the allergic, respiratory, 
enteric, and sexually transmitted diseases, the NIAID 
programs support research on most of the bacterial, fungal, 
viral, and parasitic diseases that create large problems 
in the tropical and subtropical countries of the world. 
Those diseases include leprosy, cholera, dengue, oncho- 
cerciasis, filariasis, trypanosomiasis, leishmaniasis, 
schistosomiasis, malaria, and biologic control of the 
vectors of disease. Probably the most significant con- 
tributions stem from the extensive program for research 
in immunology that supplies information on the disease 
mechanism and new and improved methods for diagnosis, 
treatment, and prevention. 

Foreign research grants, while relatively few in 
number, are of high caliber, having successfully competed 
with a large number of other grant applications, many of 
which are approved but unfundable at current budget levels. 
These include grants to foreign institutions, grants to 
U.S. institutions that fund part of the investigators' 
studies abroad (e.g., ICMR program), and collaborative 
research funded in certain countries with U.S. -owned local 
currency. During FY 1975, 17 research grants were made 
to investigators in 10 countries. The bulk of that funding 
(72.3%) was for studies in immunology. Grants awarded to 
U.S. investigators for training abroad were largely (65.7%) 
in the field of immunology. 

Tabular data on U.S. domestic research grants that 
fund a portion of the studies are not readily available. 
Funding of this type enables the research investigators 
to conduct studies in areas where the diseases under study 
are prevalent or endemic, but rare or nonexistent in the 
United States. The nature of such studies can be illus- 



79 



80 



trated by the following examples of studies conducted by 
NIAID intramural scientists. They also illustrate some 
of the studies on diseases of prime importance to other 
countries . 

Malaria 

A videotape technique for study of the invasion of 
red blood cells by malaria merozoites led to immuno- 
chemical studies of the surface receptors involved. Based 
on previous observations that Duffy negative blood group 
West Africans had greater resistance to Plasmodium vivax 
malaria, Duffy positive and negative red cells were used 
in an in vitro system with P. knowlesi , to reveal that 
Duffy positive red cells were invaded, whereas the Duffy 
negative cells were resistant. In addition, removal of 
Duffy blood group determinants by proteolytic enzymes, or 
blocking the receptors with anti-Duffy serum, markedly 
reduced invasion. These findings open the way to a search 
for similar type receptors for other species of malaria 
and possibly to exploitation of this knowledge for approaches 
to rendering red cells resistant to merozoite invasion 
as a method of treatment or prevention of malaria. 

As a WHO short-term consultant, Dr. David J. Wyler 
(LPD/NIAID) spent nearly 4 months in Gambia, West Africa, 
studying aspects of the cell-mediated immunity in malaria. 
Cases of falciparum malaria were found to have signifi- 
cantly reduced circulating T cells during acute infection. 
The finding of a ehemotactic factor for monocytes in 
splenic extracts of mice and monkeys with malaria may 
help to explain why splenomegaly is so prominent in 
malaria. A review of old data on the influence of splen- 
ectomy upon the course of established P. inui infections 
in monkeys has revealed an interesting observation that 
splenectomized animals cure themselves in contrast to 
intact animals that have chronic infections for many years. 

Filariasis 

In collaboration with the health authorities of the 
Cook Islands, South Pacific, who had scheduled antifilarial 
drug treatment of the population of the out island of 
Mauke, Drs . Eric Otteson, Louis Heck, and Peter Weller 
(LCI, LPD/NIAID) spent 4 months on the island conducting 
clinical and immunologic studies before, during, and after 
the mass treatment. Through cooperation provided by Duke 
University and TIB/NIAID, Marilyn MacQueen joined the 
field team and conducted HL-A typing of a large portion 
of the study population. The establishment of a field 
laboratory on Mauke enabled the performance of function 
tests and those possible only with fresh material. Many 
specimens were collected and preserved for serologic 



81 



and biochemical analysis in the Bethesda laboratories. 
This expedition provided an invaluable opportunity to 
correlate the laboratory and clinical observations of 
this disease and to observe the dramatic effect of die- 
thylcarbamazine in clearing the circulating microfilaria; 
90% reduction of worms in the first hour of treatment. 
Additional studies were done on the dog, rodent, and 
mosquito populations of the island. 

Dengue and Other Virus Infections 

The Pacific Research Section, LPD/NIAID, located in 
Honolulu, Hawaii, is the center for a variety of collab- 
orative studies and laboratory reference from many of 
the islands and countries in the Pacific area. These 
studies provide expert help to the health authorities of 
those areas and some unique research opportunities for 
Dr. Leon Rosen and his staff of research scientists at 
the Pacific Research Section. The following are examples 
of such studies. 

Dengue type 1 virus reappeared after 30 years on the 
Pacific islands of Nauru, Ponape, and Fiji, affording an 
opportunity to study the behavior and manifestations of 
this virus under relatively simple and known epidemiologic 
conditions. Studies were done, also, on a flare-up of 
dengue type 2 disease on Tonga and Tahiti. It was observed 
that the fatal form of the disease (hemorrhagic and shock 
syndrome) can result in individuals who have not previously 
experienced dengue infections. In collaboration with the 
SEATO laboratory in Thailand, it was demonstrated that 
two to three times as many virus isolations were obtained 
from dengue hemorrhagic fever patients by mosquito inoc- 
ulation than by conventional cell culture techniques. 
Studies of oral susceptibility to dengue virus among geo- 
graphic strains of the vector mosquito Aedes albopictus 
disclosed a similar pattern with all four dengue serotypes. 
Studies on genetic differences in susceptibility of mos- 
quito strains showed that significant changes resulted 
from selective inbreeding, but no clear-cut mode of in- 
heritance could be determined. A simple direct feeding 
technique was developed to test the ability of mosquitoes 
to transmit dengue viruses without feeding on a vertebrate 
host. 

Serum surveys of Southeast Asia and Pacific islands 
have shown that human Chikungunya virus infections are 
confined to the mainland, Indonesia, and The Phillipines. 
However, antibodies to another group A arbovirus, Ross 
River, were found in serum specimens from New Guinea and 
the Bismarck and Solomon islands. Using a plaque reduc- 
tion neutralization test, evidence of human infection 



82 



with four Phlebotomus (sandfly) fever group viruses was 
found in specimens from Greece, Iran, Egypt, Sudan, and 
Nigeria. 

Dr. Robert B. Tesh spent 4 months studying the epi- 
demiology of sandfly fever in Iran, as a collaborator 
funded by the School of Public Health, University of 
Teheran. The studies involved three geographic areas 
and were used to train Iran workers in epidemiologic 
techniques for sandf ly-borne diseases, which are impor- 
tant public health problems in the Middle East. Many 
human, animal, and insect specimens were collected and 
transported to the Pacific Research Section for laboratory 
investigations . 

Clinical Research 

During July and August 1974 Dr. Sheldon M. Wolff, 
Clinical Director, NIAID, spent several weeks in Brazil 
where he has gone each summer for the past 3 years. During 
these visits he lectures to students and faculties, sees 
patients, makes rounds, and meets with individual scien- 
tists to review work and offer advice and ideas. Out 
of these visits has grown a very close relationship 
between several of the senior faculty at the Federal 
University of Rio de Janeiro and the Clinical Director. 
For example, two senior scientists from the Institute of 
Biophysics in Rio have spent time working, and one is now 
in training in LCI, NIAID. The Clinical Director, NIAID, 
has already accepted invitations to return to Brazil next 
summer to lecture in Sao Paulo and Rio de Janeiro. 

The Clinical Director, NIAID, also spent time in 
July 1974 and again in June 1975 with collaborators at 
the Pasteur Institute in Paris, France. These investi- 
gators have prepared materials that appear to have pro- 
perties of inducing nonspecific resistance to infection, 
and this work has resulted in a paper recently submitted 
for publication. Plans are under way to eventually evaluate 
these components here at NIH in human beings. 

In June 1975 the Clinical Director, NIAID, presented 
an invited lecture at one of the major symposia at the 
International Congress of Nephrology in Florence, Italy. 
Approximately 1,500-2,000 people from all over the world 
attended this symposium. 

In August 1974 the Head, Biologic Structure Section, 
LCI, NIAID, visited a number of laboratories in South 
Africa where he presented lectures and discussed research 
with senior scientists from the University of the Witwater- 
srand and South African Society of Patholoqy (where he 
taught a course in immunology), Johannesburg, South Africa. 



83 



Dr, Charles Kirkpatrick f Head, Clinical Allergy and 
Hypersensitivity Section, LCI, NIAID, visited in March 
1975 the Rheumatic Fever Project in Cairo, Egypt, as a 
consultant. This is a collaborative project of the 
Center for Disease Control, DHEW, and the Ministry of 
Health of Egypt. 

Scientific Communications 

The NIAID is conducting two experiments for the 
development of new and improved methods for informal 
communications between research investigators. These 
involved a rapid and frequent distribution of short, 
informal, written communications, and the use of a commun- 
ication satellite. Both experiments include scientists 
from many countries and thus are international in opera- 
tion. 

The scientific memoranda contain short, informal 
progress reports on current research, scientific comments, 
and any other informal communication pertinent to the 
research subject covered. Communications are photoreduced 
and reproduced, without editorial attention, and distributed 
to the participating scientists monthly or quarterly. 
Scientists from 47 countries, plus the United States, 
participate in this project. Separate scientific memo- 
randa exist for interferon, hepatitis, leprosy, hyper- 
sensitivity disease, sexually transmitted disease, 
transfer factor, and nucleic acid recombinants. 

The satellite experiment uses the NASA ATS-1 satel- 
lite maintained in geosynchronous orbit approximately 
23,000 miles above the equator in the middle of the 
Pacific Ocean. The satellite coverage area includes the 
whole Pacific Ocean and as far east as Bethesda, Md. 
Anyone in the coverage area, equipped with relatively 
small and inexpensive FM radio transceivers with proper 
frequencies, can communicate directly via the satellite. 
The NIAID project is purposed in determining the useful- 
ness of this method of informal communication to bio- 
medical research investigators. The project has involved 
scientists on field trips or in their laboratories in 
many of the countries and island areas of the Pacific. 

Geographic Medicine Branch Program 

This Branch of NIAID manages three international 
programs: the U,S«- Japan Cooperative Medical Science, 
the International Centers for Medical Research, and the 
Cholera Research Laboratory in Dacca, Bangladesh. 



84 



U.S. -Japan Cooperative 
Medical Science Program 

The U.S. -Japan Cooperative Medical Science program 
was initiated in January 1965 as the result of a meeting 
between the Prime Minister of Japan and the President of 
the United States. The two heads of state agreed to 
undertake a greatly expanded, joint cooperative research 
effort in biomedical sciences to improve the health of 
the people of Asia. The disease categories considered 
to be of particular importance included cholera, leprosy, 
malnutrition, the parasitic diseases schistosomiasis and 
filariasis, tuberculosis, and the viral diseases rabies, 
dengue hemorrhagic fever, and other selected arboviruses. 
In 1972 environmental diseases was added as a program 
interest. 

The U.S. -Japan Cooperative Medical Science program 
operates within a bilateral government framework. Never- 
theless, it may involve scientists and facilities in third 
countries and/or collaboration with international or other 
organizations. The relevant regions in Asia, although not 
specifically defined, are generally understood to include 
the Republic of Korea on the north, India and Pakistan 
to the west, and other adjacent nations in the broad 
Pacific basin. 

The United States and Japan each support the cost of 
their own scientific projects and meetings. 

1. Cholera 

The cholera program has completed a toxoid field trial 
in some 92,000 persons in the cholera endemic area of 
Bangladesh. The fall cholera epidemic was unusually severe 
this past year and provided a most rigorous test of the 
protective effect of antitoxic immunity to El Tor cholera 
infection. The conclusion from the field trial of two 
injections of cholera toxoid (100 mg each) is that pro- 
tection from antitoxic immunity was transient with no 
improvement over licensed cholera vaccine. However, this 
toxoid produced a higher level of protection in the child- 
ren under 14 years of age than in adults. This finding 
was unlike earlier field trials with cell vaccines that 
always gave better protection in the adults and lower 
protection in children. The level of somatic antigen in 
the toxoid did not stimulate vibriocidal antibody pro- 
duction in the native population. This confirms the high 
degree of purity of this toxoid. Work now centers on how 
to enhance the limited protection seen in the first field 
trial of a cholera toxoid. 



85 



Important observations have been made on the effect 
of local immunization on resistance. Most significant is 
that if the dog model was primed with one parenteral in- 
jection of toxoid, followed in 1 month by a series of 
oral doses, there was prolonged protection against cholera 
challenge. Serum antitoxin levels, however, were notably 
low. These findings have been confirmed in rats. A 
similar dose schedule in rats called forth the maximum 
number of specific antitoxic plasma cells in the lamina 
propria of the small bowel. Local response required 
local stimulus, and it was shown that lymphocytes derived 
from gut-associated lymphoid tissue, such as Peyer ' s patches, 
passed through the thoracic duct circulation and returned 
to the small bowel in the absence of local antigen. This 
information on local immunity underlines the importance 
of further studies on the local immune mechanisms. 

A chemically induced nontoxinogenic mutant of a highlibrio 
toxinogenic strain of V cholerae has been fed to volunteers 
and found to multiply in the gut without producing disease. 
These volunteers were resistant to challenge with live 
virulent organisms. The mechanism of resistant is assumed 
to be antibacterial and the method may hold some promise 
for a future, live oral vaccine. 

Detailed studies on the structure of the cholera enter- 
otoxin molecule has indicated that there were two subunits, 
designated A and B. Subunit A, the adenylate cyclase- 
activating component of the enterotoxin molecule, is com- 
posed of two chains designated Al and A2 linked by disulfide 
bonds. Amino acid sequencing studies have been started 
in several laboratories. 

The U.S. and Japanese cholera panels have catalyzed 
a cooperative venture between the two countries to stan- 
dardize the characterization of noncholera vibrios. Two 
laboratories in each country are involved. The plan is to 
share type cultures from each country's collection and 
compare biochemical and serological results with the idea 
of arriving at a mutually agreeable classification system. 
The United States has sent 86 type cultures to Japan, and 
the Japanese have sent 38 type cultures from their collec- 
tion. The four laboratories are busily engaged in applying 
their testing schemes to these new cultures. Early results 
indicate that 31 of the Japanese cultures may be similar 
to U.S. type cultures. 

Studies on the incidence of diarrhea caused by enter- 
otoxin producing E coli are progressing well. The first 
40 cases of diarrhea studied in a pediatric hospital in 
Brazil indicates as many as 50% of the children had lactose 
fermenting organisms that produced the cholera-like, heat- 



86 



labile toxin as the only fecal pathogens. So far, very 
few E. coli have been found that produce only heat-stable 
toxin. Thus, the importance of strains that produce only 
heat-stable toxin in human disease remains unknown. The 
role of enterotoxigenic E. coli should come into better 
focus as more cases are added to the study. Material 
from these E. coli studies is also being examined for the 
rheovirus-like agent associated with some infantile 
diarrheas . 

Considerable progress has been made on isolating and 
characterizing a low-molecular-weight, heat-labile toxin 
from E. coli . The material has been extracted from the 
culture and reduced to near electrophoretic homogeneity 
by chromatographic techniques. It is active biologically 
at the nanogram level and shows strong cross reactions 
with antisera produced by purified cholera toxin. Attempts 
are under way to achieve higher yields of this material. 

2. Environmental Mutagenesis/Carcinogenesis 

Stimulation of the development of better methodology 
to screen chemicals before they are released into the 
environment, as well as to provide a thorough evaluation 
of chemicals already present in the environment, is one of 
the primary activity areas of this panel. Exploratory 
experiments on various classes of chemicals (drugs, food 
additives, pesticides, cosmetics, industrial compounds, 
etc.) have already shown that there are numerous examples 
of agents that have genetic activity in experimental 
organisms. The main question is to determine their effect 
on man. In addition, recent studies have shown that there 
is some correlation between carcinogenic and mutagenic 
activity and evidence of mutagenic activity in experimental 
organisms may mean that a chemical not only presents a 
genetic hazard to man but a carcinogenic hazard as well. 

To ensure the effectiveness of any screening program 
established, new approaches will have to be developed for 
population monitoring and epidemiology. Better tests are 
needed to evaluate the effects of accidental or deliberate 
exposure to mutagenic agents on somatic cells and germ 
cells in man. Exposure of somatic cells may induce damage 
that will make an individual more susceptible to the 
development of various types of cancer; exposure of germ 
cells may induce damage that will be transmitted to future 
generations . 

One of the major deficiencies in testing is the lack 
of assays that can be made on somatic and germ cells of 
man for the production of gene mutations. In one project 
an attempt is being made to develop an assay for gene 
mutations induced in germ cells. By using loci that pro- 
duce proteins that can be studied with starch gel electro- 



87 



phoresis, it is possible to look for "electromorphs" 
(altered proteins with different electrophoretic mobility) 
or "amorphs" (changes that result in complete loss) at 
specific loci. The program of research seeks to identify 
additional loci at which such analyses can be made so that 
numerous tests can be performed on progeny of the same 
treated animal. 

In another project the research is directed toward 
the development of an assay in mice that will permit 
assay of a random sample of loci over the entire genome. 
Development of mouse strains containing large numbers of 
inversions will permit assay of the recessive lethal 
mutations occurring in these regions. 

The development of better methods for detection of 
point mutations in somatic cells is the objective of 
another project that utilizes blood samples to determine 
the frequency of variant red blood cells. Normally, only 
a very low percentage of erythrocytes contain fetal 
hemoglobin. An assay is being developed with selective 
antisera to determine the frequencies of such variants 
quantitatively . 

The development of assays for gene mutations at spe- 
cific loci is under way in another project utilizing human 
fibroblasts in culture. This system utilizes the hypox- 
anthine-guanine phosphoribosyltransferase (HGPRT) locus 
as well as the azaguanine phosphoribosyltransferase (AGPRT) 
locus. Present data clearly indicate that drug-resistant 
mutants result from genetic changes at these two loci 
that result in structurally modified enzymes. The spon- 
taneous frequency of variants at each locus has been 
determined in various individuals as has the induced 
frequencies obtained after mutagenic treatment. 

The better detection of the genetic activity of air- 
born environmental pollutants is the objective of an 
additional project with the wildflower Tradescantia . By 
using a strain heterozygous for flower petal color, it 
is possible to observe pink and colorless sectors in 
normally blue flower petals and stamen hairs. The assay 
system is a very sensitive detector of the mutagenic 
activity of radiation, and exploratory experiments are in 
progress to determine its sensitivity to various chemicals 
including known chemical mutagens. 

The collaborative efforts of the United States in 
this program are provided through the National Institute 
of Environmental Health Sciences and the National Institute 
of Allergy and Infectious Diseases. 



88 



3. Leprosy 

The three areas of leprosy research that continue 
to receive special emphasis include immunology, chemo- 
therapy, and cultivation and transmission in animal models, 

Excellent progress has been made in preparing trans- 
fer factor (T.F.) to be used in a controlled clinic trial 
to evaluate the immunotherapeutic response of this agent 
in the treatment of lepromatous leprosy. Efficacy of 
T.F. will be determined by in vitro laboratory studies 
that measure cellular mediated immunity, as well as by 
clinical assessment to evaluate any improvement of local- 
ized lesions. It is anticipated that at least 2 years of 
continuous observation will be required to draw conclusive 
results on the efficacy of this form of immunotherapy. 

The fourth annual surveillance of post- treatment of 
leprosy patients among the Pingelapese population was com- 
pleted in February 1975. At present, the investigators 
have concluded that eradication of leprosy in an endemic 
population by use of DADDS for preventive treatment can- 
not be totally effective without simultaneous and con- 
tinous drug control of all bacilliferous cases. Studies 
will continue in FY 19 76 to determine if mass treatment 
with DADDS is associated with the emergence of sulfone- 
resistant infections. 

Studies on the in_ vitro cultivation of Mycobacterium 
lepraemurium were initiated by a research contract during 
the past year. Preliminary work has demonstrated that 
fetal calf serum is superior to goat or bovine sera as a 
supplement to Nakamura's basal medium. A thorough evalua- 
tion of the efficiency of different sera is in process. 
Other factors, such as microaerophilia and levels of 
aerobiasis, are under investigation to determine methods 
and techniques to enhance in vitro cultivation of M. 
lepraemurium . The nine-banded armadillo continues to be 
an outstanding animal model for the in vivo cultivation 
of large quantities of M. leprae . Steps have been taken 
to establish and support a continuous colony of armad- 
illos infected- with M. leprae . This potential source of 
M. leprae will provide a strong stimulus to future studies 
to ascertain the immunochemistry and antigenic properties 
of the various purified components of the organism. 

4. Parasitic Diseases 

A major breakthrough in the development of S mansoni 
culture systems for studying the growth and development 
of schistosome parasites was achieved when one of our con- 
tractors established a cell line from embryos of the 
snail host, Biomphalaria glabrata. Suitable media and 



89 



culturing techniques have been described in detail and 
are being utilized by investigators in studying larval 
stages of S. mansoni in vitro . 

Studies of the possibility of the biological control 
of schistosomiasis have shown that Biomphalaria glabrata 
snails have the potential to develop acquired resistance 
to trematode infections. This finding will make possible 
the study of the basic principles of snail immunity. 

A major granuloma-inducing antigen has been isolated 
to a single band on polyacrylamide gel electrophoresis. 
A radioimmune assay has been developed using this antigen, 
and the development of antibody against it correlates 
with the waning of granulomatous hypersensitivity. 

A joint meeting with the Japanese panel was held in 
August 1974 in Nagasaki, Japan, and a workshop on "Animal 
Models of Filariasis" was held in Bethesda, Maryland, in 
April 1975. At this workshop it was reported that four 
species of monkeys had been inoculated with a Tongan sub- 
periodic strain of Wuchereria bancrof ti resulting in 
developing worms. This was the first definitive evidence 
that W. bancrof ti , thought to be an exclusively human 
parasite, will mature in monkey hosts. This finding should 
expand the scope of filariasis research to include a wide 
variety of studies on this important human disease. 

Ultrastructural studies of the development of Brugia 
Malayi larvae in the mosquito vector's flight muscles have 
demonstrated a specialized surface that is suggestive of 
absorptive function during a phase of rapid growth and 
development. This is the first demonstration of such a 
function in filarial larvae, and it is hoped that supple- 
mentary biochemical studies will follow. 

5. Tuberculosis 

The research sponsored this past year by the tuber- 
culosis program again focused on the immunologic aspects 
of tuberculosis. The monkey model for studying aerosol 
BDG vaccination with aerosol challenge continues to be 
investigated. Previously, it was shown that the route 
of administration of BCG vaccine significantly affects the 
degree of protection against aerosol challenge with 
virulent tubercle bacilli. Inhalation of the vaccine or 
administration by the intravenous route confers a higher 
degree of resistance to challenge than does intracutaneous 
administration of vaccine. The protection afforded by 
aerosolized vaccine was also found to be related to the 
total dose of viable units administered. The highest dose 
tested, 105 (vu) was the most effective. As an adjunct to 
this study, it was found that previously sensitized guinea 



90 



pigs did not display clinical signs of pulmonary distress 
after exposure to aerosolized BCG; however, there was an 
indication of slight, but statistically significant, in- 
crease in total airway resistance following exposure. 

A study is now under way to determine the duration 
of protection afforded by aerosolized BCG as opposed to 
intracutaneously administered BCG. Deaths in animals 
challenged 8 and 28 weeks following vaccination are less 
than in the control group. Less pulmonary infiltrate is 
seen in radiographs of those animals receiving the intra- 
cutaneous vaccine. As a follow-up to the guinea pig pilot 
study with BCG-sensitized lungs, a more comprehensive 
study with monkeys has recently been initiated. 

The relationship of delayed-type hypersensitivity to 
one or more microbial antigens in the immunized host and 
the expression of cell-mediated immunity (CMI) against a 
virulent challenge organism have been clarified. It has 
been established that a sensitizing preparation must be 
used if an effective antibacterial resistance is to be 
developed. Large doses of living bacilli may induce an 
effective CMI in the apparent absence of peripheral DTH 
but transfer studies showed that the anergic animals still 
contained sensitized lymphocytes capable of transferring 
tuberculin sensitivity to normal recipients. 

Migration inhibitory factor (MIF) and a new type of 
interferon (type II) are released into the circulation 
after mice have been sensitized intravenously with viable 
BCG and challenged later with old tuberculin. In this 
in vivo production of mediators the activity of MIF was 
at least 100-fold greater than the MIF induced in_ vitro . 
Two components of BCG, the protein PPD and the lipid P3 
necessary for the production of MIF, were also necessary 
for the induction of resistance to a virulent aerosol 
challenge. In preliminary studies, the production of MIF 
in vivo in mice seems to be associated with both B and T 
lymphocytes. Other studies involving the basic immune 
mechanisms of the mycobacterioses continue. 

This year a task group convened at the National In- 
stitutes of Health to discuss the role of soluble mediators 
of cellular immunity in tuberculosis. These substances 
have been shown to be of immense biological and clinical 
importance and are the subject of widespread investigation. 
A general overview of the problem area was discussed, those 
areas where the U.S. -Japan program could provide support 
were identified, and a list of priorities to facilitate 
orderly progress of the research were developed. 

Highly characterized and standardized mycobacterial 
materials continued to be available to qualified scientists 
working in tuberculosis and related areas. 



91 



6. Viral Diseases 

Studies have established that protection from virulent 
intracerebral challenge with rabies virus is directly 
dependent on the level of specific neutralizing or lytic 
antibody present at the time of challenge. Inactivation 
of rabies virus by beta-propiolactone was evaluated by 
the rabies fluorescent focus inhibition test (RFFIT) and 
was shown to leave no detectable residual infective virus. 
The RFFIT was found to be more reproducible than the mouse 
neutralization test, requires less time for completion, 
and is less expensive. A major rabies glycoprotein has 
been extracted by exposure to alkaline EDTA. Physical 
chemical procedures attest to the purity of the glyco- 
protein preparation. This protein consists of a single 
polypeptide chain with a molecular weight of 70,000 daltons. 
Its biological activity was demonstrated by immunization 
of hamsters, rabbits, and mice. 

Recent studies on skin biopsy material from dengue 
patients indicate that skin rashes in these cases are 
likely to be immunopathologic in nature. It also has 
been shown that in acute stages of dengue hemorrhagic 
fever and dengue shock syndrome, B lymphocytes and certain 
dengue antigen antibody combinations form immune complexes 
on cell surfaces. In studies of the epidemiology of 
dengue virus in the jungles of Malaysia, it has been shown 
that dengue is a zoonosis involving wild monkeys in the 
primary rain forest. Recent emphasis has been on attempts 
to identify the mosquito species that serves as the 
important jungle vector. Evidence has been obtained showing 
that enzootic dengue, involving at least three of the 
four known virus types, occurs in the high canopy of 
isolated primary rain forest and that Aedes niveus mosquitoes 
are most likely the jungle vectors. Other vector studies 
have uncovered a marked variation in susceptibility of 
dengue viruses and the stability of this character from 
generation to generation. This could be of great impor- 
tance in controlling epidemic dengue. Results suggest that 
it might be possible to achieve disease control in an area 
by replacing a susceptible vector population with a more 
refractory strain of the same species. 

7 . Malnutrition 

Although malnutrition is one of the categories included 
under the U.S. -Japan program, this area is partially ad- 
ministered by NIAMDD and will be included as part of its 
report. 



92 



International Centers 
for 
Medical Research (ICMR) Program 

In response to the expressed desire of the Congress 
(PL 86-610) , a program for the International Centers for 
Medical Research was established in 1960 by the National 
Institutes of Health "to advance the status of the health 
sciences in the United States and thereby the health of 
the American people" by expanding collaborative research 
between U.S. universities and selected foreign institutions 
and investigators. Since 1968, this program has been 
administered by the National Institutes of Allergy and 
Infectious Diseases. 

The four grants funded under this program are awarded 
for 5 years with continued support contingent upon pro- 
gram review at the end of each year of operation. One 
of the most important features of this program is that 
of long-term support, as contrasted with the transiency 
that has characterized a number of other international 
projects. This is a necessary ingredient for the full 
development of university careers in science in order to 
effectively utilize the international medical experience 
of individual scientists. This program provides oppor- 
tunities for established and highly competent investigators 
to realize valuable research opportunities abroad without 
losing their university affiliations and faculty appoint- 
ments. The long-term support of the ICMR does not represent 
a form of foreign aid since the primary objective is a 
collaborative effort in biomedical research of specific 
relevance to the health of the American people and to 
the U.S. scientific community. The four current ICMR 
grants were renewed for an additional 5 years beginning 
FY 1975. 

1 . Purpose and Scope 

The ICMR program has as its principal objective the 
provision of high quality research and scientific oppor- 
tunities for Americans in the broad fields of geographic 
medicine and in response to the special opportunities 
existing with each ICMR framework. The length of the 
research period overseas is a discretionary concern of the 
ICMR program director and is obviously determined by both 
the interests of the prospective investigator and the 
specific opportunities available within the given ICMR 
unit. Consistently, the emphasis is upon the quality 
rather than the quantity or duration of the research pro- 
grams . 



93 



The aggregate ICMR units are serving increasingly as 
a national resource for utilization by senior, as well as 
less experienced, scientists to create a comparatively 
modest pool of investigators with a sustained career 
interest in international or geographic biomedical research. 
In this regard, the ICMR program directors are encouraged 
to establish a selective, interdisciplinary scientific 
program. Their activities encourage and accommodate a 
number of parent university departments other than the 
department that primarily sponsors the ICMR operation. 
Particular advantage is taken of special strengths within 
the overall parent university, including opportunities 
in health-related fields outside the classical confines 
of tropical medicine. As far as is possible, the ICMR 
core grant is used for research support at the offshore 
ICMR site rather than at the parent domestic university. 
In this regard, it is accepted that some preparation 
preliminary to an overseas assignment is necessary and as 
many items of equipment and supplies as feasible are 
purchased in the United States. 

Discussion of the four institutions participating in 
the ICMR program at present and their respective areas 
of research interests follows: 

1. Johns Hopkins University (Baltimore, Md.) 
Program Director: Dr. Frederik B. Bang 

Several years ago, Johns Hopkins University transferred 
its operations from Calcutta to Dacca, Bangladesh, to 
take advantage of the facilities at the Cholera Research 
Laboratory and to initiate a series of studies on Bang- 
ladesh disease problems that had been previously studied 
by the Hopkins group in India. Program emphasis continues 
to be directed toward the epidemiology and management of 
human diseases of large populations and the ecology and 
behavior of animals living in close association with man. 
Research on cholera and other diarrheal diseases consti- 
tutes the core of the program and includes studies of the 
effect of zirconium oxychloride on fluid loss, oral sucrose 
therapy, collection of toxinogenic strains of Eschlerichia coli , 
studies of leukemoid reactions and hemolytic anemia in 
shigellosis, determination of T and B cell response in 
Shigella infection, and a study of the association between 
malnutrition and diarrheal diseases. Related studies are 
directed at the effect of protein calorie malnutrition in 
immunological competence. Three programs were conducted 
during the past year on parasitic diseases: epidemiology 
of endemic filariasis; epidemiology of echinococcosis; 
and a study of local malaria vectors. 



94 



Ecological studies have been initiated to determine 
the contribution of rodents and insects to crop and store 
grain loss, to correlate the rate of fish growth with food 
sources and water quality, and to determine how to maximize 
the benefits of dung beetles, distribution of feces in 
soil, and maintenance of soil porosity. 

2. University of Maryland (Baltimore, Md.) 
Program Director: Dr. David Clyde 

The University of Maryland, with the participation 
of its School of Medicine and collaborating with the 
Institute of Hygiene, Lahore, has undertaken a varied 
research program in West Pakistan. This program during 
the past year has continued to be based on studies of the 
genetics of important insect vectors of virus and para- 
sitic diseases. The objective is production of strains 
with lessened vector ability. Associated with the inves- 
tigation of the genetics of Anopheles stephensi , a prin- 
cipal carrier of malaria in central and western Asia, has 
been an examination of the resistance of local strains of 
this mosquito to insecticides, an increasingly serious 
problem for the malaria eradication campaigns of Pakistan 
and neighboring countries. Genetic manipulation of Culex 
tritaeniorhynchus , important in the transmission of Japanese 
B encephalitis, West Nile, and Chikungunya viruses and 
ranging from East Asia to West Africa, is yielding results 
that will permit early field application on a limited scale. 

3. University of California (San Francisco, Calif.) 
Program Director: Dr. Albert Rudnick 

The University of California, with the participation 
of the Hooper Foundation, the School of Public Health, and 
the Medical School, is collaborating with the Institute 
for Medical Research, Kuala Lumpur, Malaysia and the 
University of Malaya. This international center continues 
to place strong emphasis on infectious diseases transmitted 
from animals to man. Because of the long-standing research 
interest and experience in studying the fundamental prob- 
lems of human ecology at the University of California, a 
collaborative program has been developed embracing medical 
zoology, microbiology, and parasitology. The scope of this 
collaborative endeavor has now been expanded to include 
related sociocultural research and medical genetics. 

Long-term research projects in Malaysia and California 
are based on three general laboratory programs : the Ar- 
bovirus Research Unit; the Parasitology Laboratory; and 
the Medical Anthropology and Rural Health Research project. 

The arbovirus research is focused on the epidemiology 
and ecology of dengue virus and the relationship of this 



95 



virus to mosquito-borne hemorrhagic fever. A jungle 
reservoir (monkey) has recently been demonstrated for 
dengue. The parasitologic research is based on studies 
of trematode ecology and interactions of various para- 
sites in the snail host and the ecology of Malayan pen- 
tastomes or tongue worms. The snail trematode antagonism 
studies are directed toward the biologic control of schis- 
tosomiasis, and this ICMR represents a leading world 
resource for this important field research. 

Abundance, distribution, life cycle, and ectopara- 
sites of rodents closely associated with man have also 
been studied. Work on the possible role of the Indian 
fruit bat as a reservoir of human viral infections has 
been completed. Other field studies include the inves- 
tigation of bacteria and viruses pathogenic for man in 
monkey populations. Sociocultural studies concerned with 
Malayan attitudes toward health and nutrition and the in- 
fluence of native and western practitioners of medicine 
on these attitudes have been undertaken by a number of 
variously trained, medically oriented social scientists. 

4. Tulane University (New Orleans, Louisiana) 
Program Director: Dr. Paul C. Beaver 

Tulane University, with the participation of the 
Department of Tropical Medicine and Public Health, other 
departments of the Medical School, and the Department of 
Anthropology and Sociology, has been collaborating with 
the* Universidad del Valle, Cali , Colombia. The research 
work falls into three general areas : Nutrition and meta- 
bolic diseases; Infectious diseases; and Behavioral science. 

Parasitological research includes classic life cycle 
approaches to the epidemiology of paragonimiasis, trypan- 
osomiasis, and animal malaria, taxonomic studies of 
Culicoides and tabanids, an overall study of the parasites 
of bats, and a broad program of filariasis research with 
emphasis on onchocerciasis. Two principal virological 
studies have just been initiated in cytomegalovirus and 
on patients with Guillain-Barre disease. The objectives 
of the mycology program are centered primarily on the 
systemic mycoses, especially paracoccidioidomycosis, the 
most important deep mycotic infection in Colombia. These 
studies encompass both epidemiology and immunology. 

The nutrition program at the ICMR in Cali encompasses 
a variety of research activities including studies of the 
malabsorption syndrome in protein calorie malnutrition, 
enterobacteriology of protein calorie malnutrition, thyroid 
function studies in adult malnutrition, evaluation of 
protein quality for children, and a study of the nutrition 
and feeding habits of a community. A related study has been 
concerned with immune responsiveness in normal and mal- 



96 



nourished infants. 

Currently, the behavioral science program is empha- 
sizing shorter-term, small projects in five areas: social 
psychiatry and behavioral disorders; evaluative research 
and health systems; medical anthropology; social demo- 
graphy; and health service utilization. 



Cholera Research Laboratory, 
Dacca, Bangladesh 

The Cholera Research Laboratory (CRL) , Dacca, Bang- 
ladesh, continued operations during fiscal year 1975, 
financed principally by the Agency for International De- 
velopment (AID) . Through a participating agency agreement, 
the National Institute of Allergy and Infectious Diseases 
(NIAID) provided both the administrative and scientific 
support to the CRL. In addition to this staff support by 
NIAID, the Center for Disease Control deputes two EIS 
officers to Dacca; the Government of Bangladesh provides 
space in the Institute of Public Health and the Rural 
Health Center in Matlab Thana, plus utilities and a cash 
contribution. The governments of Australia and the United 
Kingdom have also contributed funds, equipment, and 
services to the CRL. 

The research program at CRL centers around diarrheal 
research involving field studies and clinical research. 
The past year demonstrated the capabilities of the CRL to 
handle a large field trial involving over 90,000 persons 
in a test of a cholera toxoid. The number of cases of 
cholera during the fall epidemic provided an excellent 
test of antitoxic immunity against cholera. The protection 
was of a low level and transient with no improvement over 
licensed cholera vaccine. Of particular interest was the 
higher level of protection in the children under 14 years 
of age. This was directly opposite to early cholera 
vaccine trials that demonstrated the lowest protection in 
children and highest in adults. Methods of improving this 
protection are being sought. The field trial population 
will remain under surveillance to measure the effect of 
the toxoid on the second cholera season. 

The development of the oral electrolyte solution for 
treatment of dehydration has received worldwide acceptance. 
However, the difficulty of finding glucose for the formula 
is a problem in some areas of the world. Further testing 
at CRL has found that contrary to earlier data, sucrose 
appears to be as effective in aiding electrolyte absorption 
as glucose. A new formula including sucrose is being 
tested in diarrhea patients. 



97 



The studies measuring the effect of a low pH and 
fluid secretion in the small bowel have revealed the rapid 
loss of the villous tips lining the small bowel. It is 
assumed that the sudden reduction in fluid loss is due 
to removal of these toxin-activated cells that are hyper- 
secreting. Animal studies are continuing, and a clinical 
protocol has been submitted for approval. The value and 
practicality of this treatment have not been firmly 
established yet. 

In a study of 50 patients with diarrhea of unknown 
etiology, nearly one third were found to have toxigenic 
Escherichia coli present in the bowel. In addition to the heat- 
labile toxin found in other toxigenic E. coli studies, 
there were two strains of E. coli producing only the heat- 
stable toxin. This is the first recognition in Bangladesh 
of an E. coli strain that produces only the heat-stable 
toxin. Its relation to disease production in man is not 
yet known. 

Shigellosis continues as a major problem in Bangladesh. 
In addition to the leukomoid reaction in severe cases, 
one third to one half these cases also develop acute 
hemolytic anemia associated with erythrocyte fragmentation. 
Blood transfusions will correct the anemia, but the patho- 
genesis remains unknown. It was also noted that shigella 
infection causes a depression of the percentage of T 
cell rosette-forming lymphocytes, while B cells remain at 
normal levels. In addition, there is a large population 
of cells not countable as T or B cells. These "nil" cells 
amounted to 10 to 60 percent of the total lymphocytes, 
compared with 3 percent in normal individuals. It is not 
certain whether these "nil" cells are another type of 
lymphocyte, immature lymphocytes, or a new undescribed 
cell. 

Over half of all patients coming to CRL hospitals are 
seriously malnourished. The CRL is taking advantage of 
this fact by studying the effect of malnutrition on diar- 
rheas. The malnourished patients, on the average, purged 
longer than comparable patients in better nutritional 
status. There was no noticeable effect on volume/unit 
of time. This extended period of diarrhea may be due to 
the prolonged life of the mucosal cells activated by 
cholera toxin in patients with malnutrition. Another study 
was designed to relate malnutrition and infection through 
cell-mediated immunity. The children below the 50th per- 
centile of Matlab standards for weight and height have 
twice the incidence of allergy as children above the 50th 
percentile. This suggests that cell-mediated immunity 
status may be an important independent determinant of 
diarrhea in addition to nutritional status. 



98 



The demographic data available from the 250,000 
persons in the surveillance area are being recognized as 
a unique data base unavailable in any other developing 
country. With the continuing census information, it is 
possible to do rate studies in this population that 
cannot be done in other developing countries due to the 
lack of a definitive denominator. A 3 year study on the 
effect of birth control measures is under way. 



NATIONAL INSTITUTE OF ARTHRITIS f 
METABOLISM, AND DIGESTIVE DISEASES 



U.S.-U.S.S.R. Cooperative 
Science Agreement 

A memorandum of scientific cooperation between 
Soviet and U.S. rheumatologists was signed May 22, 1975, 
at the National Institutes of Health. Dr. Ronald W. 
Lamont-Havers , then Acting Director, NIH, and a specialist 
in the rheumatic diseases, and Professor V. A. Nassonova, 
Director, Institute of Rheumatism, Moscow, signed an 
agreement to formalize the continued exchange of scienti- 
fic data and personnel in the field of arthritic diseases 
between these two countries. 

This agreement, the third in a series of cooperative 
memoranda signed last year in Moscow, culminated 5 days 
Of intense discussion on two major areas: evaluation of 
different methods of drug treatment for rheumatoid 
arthritis (RA) and systemic lupus erythematosus (SLE) , 
the latter an autoimmune disorder of the connective tissue 
that affects the structure and function of skin, joints, 
and internal organs; and microbial and immunologic 
studies of RA and SLE. 

Through a series of bilateral exchanges of scientific 
personnel, the program will emphasize studies of anti- 
viral, humoral, and cellular immunity in SLE and RA and 
the exchange of information in immunologic and other 
research methods. In addition to these and other planned 
activities, reprints and lectures pertinent to problem 
areas will continue to be exchanged. A symposium to 
evaluate preliminary results and plan future projects is 
scheduled for Moscow, late summer 1976. 

The cooperative study of the arthritic diseases is 
the fourth major collaborative undertaking in the health 
sciences between the United States and the U.S.S.R. 
Earlier agreements, including those in vascular diseases, 
cancer, and environmental health, were begun under the 
initial 1972 agreement on cooperation in the field of 
medical science and public health. 

The accord was formulated by the Soviet delegation, 
including Professor Nassonova and colleagues Drs. A. 
I. Speransky and M. M. Ivanova, and U.S. scientists headed 
by Drs. Lamont-Havers, William Batchelor, and Alfred 
Steinberg, NIAMDD. 

99 



100 



Nutrition Studies in South America 

In the area of malnutrition and its possible effect 
on mental development, Dr. Adolpho Chavez and associates 
(Mexico City) have documented the nutritional, sociologic, 
psychologic, and environmental factors surrounding their 
subjects to determine their influence on physical and 
mental development. At the end of 3 years, the investi- 
gators have been able to demonstrate that mothers given 
food supplements produce more milk and thus maintain 
a nutritionally adequate plateau for at least 24 weeks 
after delivery. Significantly, the physical activity of 
children who received food supplements was higher and 
became increasingly elevated after the first year, reaching 
a level six times higher than that of the unsupplemented 
group by 2 years of age. Furthermore, the unsupplemented 
group showed a 20-week retardation in neurologic development 
in the lower extremities and had lower scores in language 
ability. Both groups suffered a similar number of 
infections, but the total number of days of illness and 
the severity of the infections were significantly higher 
in the unsupplemented group. 

In other studies of malnutrition and infection, Dr. 
Leonardo Mata of the Institute of Nutrition of Central 
America and Panama has documented the high incidence of 
bacterial and viral infections and infectious diseases 
of all types, including malnutrition, in children living 
under conditions characteristic of developing countries. 
Dr. Mata's graphic demonstration of the association between 
frequency of infections in preschoolers and their impaired 
physical growth and development led him to conclude that 
weight at birth is the best predictor of child survival. 
Only 2 of 81 infants weighing at least 2,750 grams at 
birth died within the first 6 months; no deaths were 
recorded among babies weighing 3,000 or more grams. 
Survival rates decreased sharply with lower birth weights. 

Because these deaths largely resulted from diarrheal 
or respiratory disease, they were attributed in the main 
to decreased resistance to infection. There was evidence 
that the effect on the fetus of the mother's malnutrition 
during pregnancy was mediated through a higher frequency 
of intrauterine infections, as judged by levels of 
immunoglobulins in blood samples taken from the infants 
at birth. 

These observations have awakened widespread interest 
in the relationship between maternal nutrition and infant 
birth weight with subsequent morbidity, mortality, and 
physical growth, as influenced by the interactions of 
malnutrition with infection in mother and child. 



101 

U^S,^- Japan Cooperative 
Medical Science Program 

Specific research projects, carried out abroad 
among populations with nutritional deficiency diseases, 
are designed to find solutions to complex malnutrition 
problems. These projects are largely funded through 
the U.S. -Japan Cooperative Medical Sciences program and 
through the Public Law 480 foreign currency program using 
U.S. -owned local currencies derived from the sale of surplus 
agricultural commodities in developing countries. Only 
half the earth's population maintains an adequate diet, 
indicating a critical need for research to find techno- 
logic ways and means to transform marginal nutrition and 
overt nutrition deficiency to adequacy. 

Traditionally, the National Institute of Arthritis, 
Metabolism, and Digestive Diseases has conducted nutrition 
research in developing countries because of the availability 
of large population groups afflicted with specific 
nutritional deficiences that can be readily studied. The 
results from such research are twofold: It may stimulate 
emergence to self-sufficiency from mere subsistence in 
Southeast Asian countries, as well as add to knowledge 
concerning normal nutrition and nutritional requirements 
that will benefit the U.S. population. 

The startling realization that malnutrition can, 
in fact, exist within our own population lends an element 
of expediency to nutrition research. By providing scienti- 
fic .know-how for effective utilization of economical, 
indigenous protein sources, these programs also discourage 
dependency of developing countries on the United States 
for provision of expensive protein-rich foods and enable 
them to make inroads against endemic protein malnutrition. 

The mission of the malnutrition segment of NIH's 
U.S. -Japan Cooperative Medical Sciences program is to 
support both basic and applied research aimed at practical 
solutions to nutrition-related problems in the countries 
of South East Asia and other nations in the Pacific area. 

The substantial grant and contract program has already 
brought about significant findings that will help to 
improve the protein level of rice, the principal food of 
60 percent of mankind. Ordinary commercial rice lacks 
sufficient protein for normal growth and development of 
children maintained on a predominantly rice diet; in 
addition, it does not protect the adult population from 
serious protein undernutrition. 

Research identified approximately 100 rare rice 
varieties that contain from 13 to 17 percent protein in 
contrast to the conventional level of 7 1/2 percent in 



102 



currently available commercial rice varieties, A 
vigorous plant breeding program has been started with the 
aim to develop a variety of high-protein rice that has all 
the necessary additional qualities (such as disease resist- 
ance, high yield per acre, identical taste and mouth-feel 
as conventional rice) that would make possible and 
commercially feasible large-scale planting and distribu- 
tion of high-protein rice. 

In the future, however, because of a change in the 
protocols of the U.S. -Japan program, the agricultural 
portion will no longer be .supported by NIH funds. While 
the human nutrition aspects of this project will continue 
under the auspices of NIAMDD, the International Rice 
Research Institute in Los Banos, Philippines, has assumed 
responsibility for agricultural experimentation. 

Studies of the distribution, importance, and methods 
of control or elimination of natural toxic substances in 
legumes and other plant foods focused primarily on the 
distribution of mycotoxin in the food supply of Asian 
countries and its relation to human disease. The principal 
work, supported by a contract with Drs. Gerald Wogan and 
Ronald Shank of the Massachusetts Institute of Technology, 
has now been concluded. Their studies resulted in the 
publication of 15 scientific papers documenting the 
widespread occurence of aflatoxin and other mold toxins 
in Asian foods and their probable association with liver 
damage in those who habitually consume foods contaminated 
with such toxins. 

The investment in a large nutritional research 
center in Chiang Mai, Thailand, has yielded a significant 
amount of data in two priority areas of the U.S. -Japan 
program — nutritional anemia and interactions of malnutri- 
tion and infections. In studies by center personnel, 
almost 80 percent of the more than 1,500 children attending 
the hospital ' s outpatient department were found to be 
iron deficient and responded completely to iron therapy. 
In a companion study, 3,2 30 pregnant women were surveyed 
for hematologic status: 70 percent were iron deficient; 
20 percent, folic acid deficient; and 13 percent had 
combined deficiencies. Of particular interest was one 
case of pernicious (Addisonian) anemia discovered during 
the study — the first reported in a Thai. 

The latest study reported from Chiang Mai explored 
the role of varying amounts of protein and calories on 
the hematologic responsiveness of children with protein- 
calorie malnutrition (PCM) . In this investigation, the 
addition of protein and calories elicited a therapeutic 
response, with protein recording the greater effect. 
Part of this action is thought to be related to the 
responsiveness of erythropoietin (a glycoprotein considered 



103 



to be the humoral plasma factor that stimulates red cell 
production in the bone marrow) to protein feeding. 

Bladder Stone Disease in Thailand 

Bladder stone disease is one of the most serious 
health problems in northern Thailand, occurring primarily 
among village children 5 years of age and under. Research 
by NIAMDD grantees Drs. Aree Valyasevi and Sakorn 
Dhanamitta indicates that oxalcrystalluria (excessive 
amounts of crystalline oxalic acid salts in the urine) 
was commonly found in urine samples of villagers, but 
only rarely in specimens of city dwellers. Moreover, 
calcium oxalate was shown to be one of the main constituents 
of the urinary stones. 

A dietary survey showed that the villagers daily 
consumed several kinds of local vegetables and leaves of 
forest plants not eaten by the townspeople. Further 
study revealed that these food items such as tampala 
and bamboo shoots were high in oxalic acid content, possibly 
leading to the heavy oxalcrystalluria and crystal clumping, 
particularly among children. 

To counteract this occurrence, the investigators at 
Ramathibodi Hospital in Bangkok administered oral doses 
of orthophosphate, which eliminated almost all crystalluria 
and crystal clumping in the patients studied. 

The researchers concluded that in all future studies 
on the origin of bladder stone disease, external sources 
of oxalic acid (which heretofore had not received as 
much attention as the possibility of metabolic abnormali- 
ties) should be an important consideration. 



NATIONAL INSTITUTE 

OF 

CHILD HEALTH AND HUMAN DEVELOPMENT 



Nutrition 



The National Institute of Child Health and Human 
Development (NICHD) is conducting a series of coordinated 
studies on nutrition and mental development. The largest 
of these is a contract-supported study begun in 1964 in 
cooperation with the Institute of Nutrition of Central 
America and Panama and the Pan American Health Organization. 
The data from four small rural villages in Guatemala 
indicate that consumption of a dietary supplement by under- 
nourished pregnant women may increase birth weight of 
babies to approximately the birth weight observed in more 
favored populations. Infant mortality also has been 
reduced by this supplementation. Preliminary data suggest 
there may also be some beneficial effects on early be- 
havioral development. 

In a smaller grant-supported study under way at the 
Institute for Mother and Child in Mexico, food supplemen- 
tation of the mother and infant has greatly increased the 
level of activity and alertness of the infant. In addition, 
it has increased the interaction between the mother and 
her child. 

Two other projects are under way in Colombia in 
cooperation with U.S. universities. The first utilizes 
regularly available food items to improve the diet of 
pregnant women or children in urban Bogota. The Colombian 
Institute of Nutrition specialists and scientists from 
Harvard University are seeking to determine when the 
supplementation program should be introduced in order to 
effect optimal changes in growth, health, and behavior 
of the offspring. The second Colombian project is under 
the direction of a research team from Northwestern 
University and the Universidad del Valle in Cali, Colombia. 
These studies focus on undernourished preschool children. 
The data suggest that both nutrition intervention and an 
educational stimulation program may be necessary to over- 
come the deleterious effects of early malnutrition. 

Still another project is under way through the 
University of Santiago, Chile. This study is seeking to 
clarify the complex interrelationships among malnutrition, 
maternal IQ, and other social variables that influence a 
child's mental development. 

Using money allocated from the U.S. -Japan Cooperative 
Medical Science program, another NICHD joint project with 

105 



106 



the Institute of Nutrition of Central America and Panama, 
consisted of a 9 year longitudinal study of nutrition, 
infection, and growth among pregnant and lactating women, 
infants, and children of a small native village in 
Guatemala. A monograph summarizing these findings will 
soon be published. 

Another joint NICHD-Institute of Nutrition of Central 
America and Panama project consists of two concurrent 
studies on the ecology of infection, malnutrition, and 
growth of children in two Guatemalan Indian villages. 
One study seeks to determine whether the antibacterial 
defenses of the newborn are influenced by maternal nu- 
trition status, birthweight, and general health status 
of the infant. The second study is assessing the ability 
of malnourished children to elicit and maintain appro- 
priate humoral antibody response to measles vaccine and 
natural measles infection. An ongoing project funded by 
the Office of Nutrition of the Agency of International 
Development provides nutritional supplementation to the 
families of one village; a second village serves as a 
control . 

Population Research 

The Center for Population Research (CPR) of the NICHD 
has several important contracts and grants with insti- 
tutions outside the United States, some of which are des- 
cribed here. As part of its efforts to develop a variety 
of safe and effective contraceptive methods for both men 
and women, CPR supports studies at Laval University, 
Montreal, Quebec, Canada, to synthesize chemical analogs 
of steroidal antifertility compounds and in an effort 
to identify the chemical factor in the testicles that 
regulates spermatogenesis, CPR has contracted with the 
University of Trondheim, Norway. 

Under contract from the CPR the Medical Information 
Center at the Karolinska Institutet, Stockholm, Sweden, 
supplements and enhances bibliographic data available 
through the National Library of Medicine in the biological 
and medical fields relevant to human reproduction. The 
Human Reproduction Thesaurus produced by the center includes 
citations to journal articles, technical reports, mono- 
graphs, and symposia not previously included. 

As part of its program to evaluate the long-term 
effects of vasectomy, the CPR has contracted with the 
Netherlands Cancer Institute, Amsterdam, to study human 
sperm antigens and the development of antibodies in 
naturally infertile and vasectomized men. A new antigen 
from human sperm, the "swollen sperm head antigen," has 
been demonstrated in sera of vasectomized men, and its 
possible medical significance is being investigated. 



107 



To evaluate the effect of oral and other contracep- 
tives on congenital abnormalities and outcome of pregnancy, 
a research project is being supported with the Hebrew 
University-Hadassah Medical School in Jerusalem, Israel. 
This study will measure the effects of contraceptives used 
prior to and at the time of conception on outcome of 
pregnancy, especially the incidence of congenital defects 
and chromosome aberrations. 

A contract with the Mario Negri Institute of Phar- 
macological Research in Milan, Italy, supports a wide 
range of studies of the effects of currently used contra- 
ceptive steroids in laboratory animals. This project is 
part of a program designed to define better animal models 
for predicting possible adverse reactions to these agents 
in women . 

In the behavioral sciences, a grantee at the Hebrew 
University, Jerusalem, Israel, is studying the conditions 
that affect fertility patterns in Israel among Arab and 
Jewish populations. 

Another project in the behavioral sciences is analyzing 
census and national longitudinal survey data to determine 
the relationship between urbanization/migration and fer- 
tility in Thailand. The high fertility and low mortality 
characterizing Thailand place its population among the 
fastest growing in the world. In analyzing such data 
this study will add another perspective to the under- 
standing of influences upon fertility behavior. 

Remedial Learning 

Under a grant from the NICHD, a team of investigators 
in Israel have developed a highly successful and innovative 
program that has significantly improved the mental per- 
formance and learning skills in adolescent, low-functioning 
immigrant children from markedly disadvantaged cultural 
backgrounds. Departing from standardized intelligence 
tests and question-and-answer methods as an assessment 
device, the investigator has developed a "learning poten- 
tial assessment device" in which the tester trains the 
child to learn principles underlying problems - to make 
analogies and inferences. Through this dynamic inter- 
vention process, the child overcomes deficient ways of 
functioning and his progress offers diagnostic insights 
into how much he can be helped. 

Once the child's potential has been ascertained, he 
begins a system of carefully graded exercises (instrumental 
enrichment) designed to stimulate his curiosity, to enable 
him to compare different aspects of his environment, 
and to categorize and think about his behavior. By 
contrast, teaching techniques in the United States for 



108 



children with learning disabilities are concentrated 
primarily on the learning of skills and transmission of 
knowledge. 

This approach has been widely adopted with remarkable 
success by the Israeli school system and in special mili- 
tary training units for illiterate and educationally 
retarded youth. Although data are not yet fully reported, 
hundreds of disadvantaged youths have successfully com- 
pleted school and gone on to lead useful, constructive 
lives. Through a series of seminars, American and Canadian 
scientists are beginning to apply and test these techniques 
in their own research facilities and classrooms. 

This project is now in its final year of operation 
and data analysis. The investigator is near completion 
of a manuscript for book publication (in the United States) 
in which the theoretical rationale underlying his diag- 
nostic and intervention methods and instrumentation will 
be elaborated for application in this and other cultures. 
There is a strong possibility that the techniques developed 
in this project could have direct relevance to seriously 
disadvantaged populations in the United States. 

Sudden Infant Death Syndrome 

The NICHD is supporting three foreign studies of the 
sudden infant death syndrome (SIDS) . An animal model for 
the study of SIDS is being developed at the Nuffield In- 
stitute for Medical Research, University of Oxford, England. 
The Oxford investigators had previously found that certain 
liquids, such as water, sugar water, cow's milk, human 
and artificial milks, would trigger apnea (periods of 
nonbreathing) in newborn lambs. Under contract with the 
NICHD, these investigators are studying how the larynx 
and its nervous control may relate to the arrest of 
breathing in fetal and newborn lambs and kittens ; parti- 
cularly, what effects do fluids such as water (with and 
without sugar) and milk have on closure of the upper air- 
way? So far the investigators have found that at a certain 
stage in development kittens are more vulnerable to the 
fluid stimulus. They have identified two nerve receptor 
areas in the upper airway of the kittens that seem to be 
involved in the fluid-triggered apnea response. 

Pursuing a lead that SIDS may result from inadequate 
lung responses, a grant-supported study at the Hospital 
for Sick Children in Toronto, Canada, is exploring the 
hypothesis that some infants' lungs cannot respond to 
stress on their respiratory system and that this might 
contribute to the occurrence of SIDS. A Canadian scientist 
is taking measurements of breathing activity, such as 
mouth pressure, lung capacity, and frequency of inspiration/ 
expiration in newborn and older infants. Calculations with 



109 



these data should produce a method of measuring the elas- 
ticity and strength of the respiratory system of the newly 
born and young infant. 

A contract with the University of Toronto, Canada, 
supports studies to characterize the effects of respira- 
tory tract sensory feedback on the respiratory behavior 
of adult cats and kittens. A particularly striking 
observation has been that the activity of only 50 percent 
of the rhythmically active neurons in the adult could be 
suppressed by peripheral sensory feedback, while the 
discharge of all similar cells so far tested in the kitten 
was suppressed. Differences have also been found in 
excitory input between the adult and infant animals. These 
preliminary findings that the suppressive effect of the 
upper airway feedback on ventilation is greater in young 
animals appear highly relevant to the etiology of SIDS. 

Processes Basic to Reading 

The NICHD currently supports an unusually interesting 
and potentially important study in the basic reading 
processes in Yugoslavia. A number of different experiences 
are being conducted that focus on the basic information- 
processing steps involved in letter and word recognition. 
These experiments take advantage of the fact that Serbo- 
Croatian, the language of Yugoslavia, uses two ortho- 
graphies (alphabets) ; both the Cyrillic and the Roman 
alphabets are entirely phonetic and each is read with 
equal facility by many Yugoslavs. The research exploits 
this situation, making possible detailed comparisons with 
similar studies conducted with English speakers at U.S.- 
based laboratories under TSIICHD support. The emphasis in 
this research is on the units of recoding from visual to 
phonetic form and on the linguistic level at which visual 
inputs merge into the processes of speech. For example, 
in one experiment subjects are shown successive tachisto- 
scopic (flash projector) presentations of letters (Roman- 
Roman, Roman-Cyrillic, etc., a procedure designed to 
create a masking effect; subjects must attempt to identify 
the letters. The institute anticipates significant, new 
information from studies of this type that will lead to 
a better understanding of the normal reading process and 
those factors that interfere with or prevent many children 
from acquiring this essential skill. 



NATIONAL INSTITUTE 
OF 
ENVIRONMENTAL HEALTH SCIENCES 



U.S.-U.S.S.R. Medical Science and 
Public Health Cooperative Agreement 

Under the public health part of the U.S.-U.S.S.R. Coop- 
erative Health Agreement, NIEHS and several other American 
research institutes have developed a collaborative research 
program with several Soviet scientific institutes to 
explore three problem areas in environmental health: the 
methodologic basis to assess the biologic effects of in- 
haled chemicals; the methodologic basis to assess the bio- 
logic effects of orally introduced chemicals; and the 
scientific basis to assess the complex biologic effects 
of chemicals inhaled and introduced orally. These three 
problem areas are subdivided into eight specific research 
subjects. U.S. participation in this effort is under the 
overall coordination of the director, NIEHS. 

1975 was the third year of formal cooperative efforts 
in environmental health between the United States and 
U.S.S.R. The first year was concerned largely with estab- 
lishing working relationships and agreeing on areas of 
joint study. Initiation of joint research efforts began 
in the second year of the agreement and involved exchange 
visits between scientists of both sides. 

In December 1974, U.S. and Soviet researchers partici- 
pating in the agreement met at the invitation of the Soviet 
government in Riga, Latvia, to present the results of 
their cooperative effort to date. Five NIEHS scientists 
attended this meeting. The results of this symposium will 
be published in 1975 in both the United States and the 
Soviet Union. A cooperative research program for 1975-1976 
was agreed upon during the Riga symposium. 

By the end of 1975, over 20 scientific papers will have 
been published by U.S. and Soviet scientists on environ- 
mental health research conducted under the auspices of 
this agreement. 

An initial draft of a Russian-English glossary of en- 
vironmental health terms was prepared during 1974 and is 
currently under review by both countries. A first edition 
of this glossary will be published in 1975 in both countries 



111 



112 



U t S."U.S,S.R t Agreement on Cooperation 
in the 
Field of Environmental Protection 



NIEHS participation in this agreement, which spans 
the most significant aspects of problems of the environment, 
is focused on the area of the "biologic and genetic 
effects of pollutants." The director, NIEHS, serves as 
HEW representative to the Environmental Protection Agree- 
ment and as co-chairman of the working group for the problem 
area concerned with the biologic and genetic effects of 
pollutants. Cooperation in this area, involving scientists 
from NIEHS, EPA, and university laboratories, is focused 
on the mutagenicity of environmental contaminants, the 
toxic effect of heavy metals in the environment, psycho- 
physiologic factors, and epidemiology. Program activity 
in 1975 consisted largely of information exchange and a 
joint workshop in New York City in April on "Basic and 
Practical Approaches to Environmental Mutagenesis and 
Carcinogenesis. " 

Investigation of Inhaled Pollutants 
under the U.S. -French Agreement 
for Scientific Cooperation 

In fulfilling its responsibilities under the agreement 
reached between NIH and the Institut National de la Sante 
et de la Recherche Medicale (INSERM) in May 1970, the 
National Institute of Environmental Health Sciences 
sponsored Dr. N. LeRoy Lapp, Appalachian Laboratory for 
Occupational Respiratory Diseases, NIOSH, during his ex- 
change visit to Dr. Sadoul's laboratory in Nancy, France, 
from September through December 1974. 

NIEHS has reviewed its participation in the program 
and has recommended that further participation by NIEHS 
be discontinued with the proviso that in the future, as 
priorities and resources allowed, NIEHS would again like 
to be an active participant. 

U.S. -Japan Cooperative Medical 
Science Program 

Dr. Charles Langley, Environmental Mutagenesis Branch, 
NIEHS, attended the Third Joint Conference of the Panel 
on Methods for Evaluating Environmental Mutagenesis and 
Carcinogenesis in Tokyo, Japan, August 1974. 



113 



Cooperation with the 
World Health Organization 



NIEHS has continued its cooperation with WHO in several 
activities. Dr. Hans L. Falk, Associate Director for 
Program, NIEHS, attended the first WHO conference on the 
"Assessment of Potential Health Hazards from Technological 
Developments," held in Geneva, September 1974. Dr. Falk 
is involved in preparing a follow-up series of inter- 
national conferences, sponsored jointly by WHO and NIEHS, 
on health hazards resulting from established or newly 
developed technologies. The first of these conferences, 
dealing with the rubber and plastics industries, will be 
held at NIEHS during fiscal 1976. 

A WHO program to prepare international health criteria 
documents on important environmental pollutants has pro- 
duced over a dozen documents that have been directed to 
NIEHS for comment and evaluation. 

Dr. Falk has been involved in the planning of a manual 
on the evaluation of the toxicity of chemicals, including 
the preparation of a chapter on modifying factors, mech- 
anisms of potentiation, and antagonism, for completion in 
early 1976. 

Dr. Falk represented WHO at the meeting on "Impact of 
Production and Use of Energy on the Environment" sponsored 
by the United Nations Environmental Program (UNEP) in 
New York, February 19 75. 

Dr. Robert L. Dixon, Chief, Environmental Toxicology 
Branch, NIEHS, met with the task group of the WHO Expanded 
Programme of Research, Development and Research Training 
in Human Reproduction in Geneva during November 1974 for 
the review of applications for research grants. Dr. Dixon 
also participated in the WHO/FDA coordination of toxicology 
guidelines for intracervical devices in January 1975. 

Dr. Robert E. Staples, Environmental Toxicology Branch, 
NIEHS, attended a meeting of the WHO Teratology Task Group 
in London during January 1975 to discuss teratology of 
medicated and nonmedicated IUDs. 

Drs. H. V. Mailing and George Mohn, Environmental Mu- 
tagenesis Branch, NIEHS, participated as members of a 
working group on the "Evaluation of Carcinogenic Risk of 
Chemicals to Man" in Lyon, France, April 19 75. 

To facilitate further cooperation between NIEHS and WHO, 
the WHO has begun to take the necessary steps toward 
officially naming NIEHS a WHO cooperating center. 



114 



In cooperation with the International Agency for Research 
on Cancer (IARC, Lyon, France, a sister organization of 
WHO) , Dr. Falk has been involved in the preparation of 
monographs on the evaluation of carcinogenic risk of 
chemicals to man. Dr. Falk has prepared background doc- 
uments on four chemicals and their derivatives : asiati- 
coside, cantharidin, carrageenans , and cholesterol. 

Seminars Sponsored by NIEHS 

Dr. F. Oesch, Department of Pharmacology, University 
of Basle, Switzerland, presented a seminar entitled, 
"Epoxide Hydrases : Inducible Enzymes Involved in the 
Inactivation of Carcinogenic and Cytotoxic Metabolites 
Derived from Aromatic Olefinic Compounds," July 1974. 

Dr. H. Uehleke, Institute of Pharmacology, University 
of Tubingen, West Germany, presented a seminar entitled, 
"The Metabolism of Haloalkanes and Their Covalent Binding 
to Tissue Macromolecules , " August 19 74. 

Dr. B. Ketterer, Middlesex Hospital Medical School, 
London, England, presented a seminar entitled, "Studies 
of Ligandin and Glutathione-S-Aryl Transferase Activity 
in Rat Liver Cytosol," September 1974. 

Professor P. Armitage (London School of Hygiene and 
Tropical Medicine), Dr. P. Lee (Tobacco Research Council 
Labs, England), and Dr. R. Peto (Oxford University, England) 
made presentations at the NIEHS Wrightsville Beach Con- 
ference on "Extrapolation of Risks to Man from Environ- 
mental Toxicants on the Basis of Animal Experiments," held 
at Wrightsville Beach, North Carolina, September 1974. 

Dr. M. Ahmad, Institute of Biology, Islamabad, Pakistan, 
presented a seminar entitled, "A Trystophanyl tRNA 
Synthetase Mutant in Neurospora crassa , " October 1974. 

Professor C. Rappe , Department of Chemistry, University 
of Umea, Sweden, presented a seminar entitled, "Environ- 
mental Chemistry of Some Chlorinated Hydrocarbons, November 
1974. 

Dr. G. M. Holder, University of Sydney, Australia, pre- 
sented a seminar entitled, " In Vitro Metabolic Studies of 
Benzo(a) pyrene in Rat and Mouse by Liquid Chromatography," 
November 197 4. 

Dr. B. Charlesworth, University of Sussex, England, 
presented a seminar and discussed research programs, 
February 197 5. 



115 



Dr. D. V. Parke, Department of Biochemistry, University 
of Surrey, Guildford, England, presented a seminar entitled, 
"Recent Developments on Biphenyl Hydroxylation as a Model 
Enzyme System for Monitoring Carcinogens," March 1975. 

Dr. T. Matsushima, National Cancer Center Research 
Institute, Tokyo, Japan, presented a seminar entitled, 
"Effects of Microbial Protease Inhibitors on Carcino- 
genesis and Metastasis," March 1975. 

Dr. E. Evans, Sir William Dunn School of Pathology, 
Oxford, England, presented a seminar on "The Cytogenetics 
of Inversions in Mice," March 1975. 

Eight foreign scientists participated in the workshop 
to discuss international coordination of research in 
environmental mutagenesis, May 1975: Dr. C. Ramel, 
University of Stockholm, Sweden; Dr. P. Oftedal, University 
of Oslo, Norway; Dr. Y. Tazima, National Institute of 
Genetics, Sizouka-Ken, Japan; Dr. B. Bridges, University 
of Sussex, Brighton, England; Dr. N. Loprieno, Institute 
of Genetics, Pisa, Italy; Dr. U. Ehling, Institute for 
Biology, Munich, West Germany; Dr. K. Sundaram, Bhabha 
Atomic Research Center, Bombay, India; Dr. H. Boehme , 
Inst. Fuer Kultur-Pf lazenforschung , Gatersleben, East 
Germany. 

Dr. R. Fahrig, Central Laboratory for Mutagenesis, 
Freiburg, West Germany, presented a seminar entitled, 
"A Mammalian Mutagenicity Spot Test: Induction of Genetic 
Alterations in Pigment Cells of Mouse Embryos with X-Rays 
and Chemical Mutagens," May 1975. 

Dr. W. Muller, Bielefeld University, West 
Germany, presented a seminar entitled, "Base and Sequence 
Specificity of DNA-Complexing Agents," June 1975. 

International Visits of NIEHS Staff 

July 1974 

Dr. J. McKinney presented a paper at the Third Inter- 
national Congress of Pesticide Chemistry in Helsinki, 
Finland. Dr. McKinney also visited the laboratories of 
Dr. G. T. Brooks, University of Sussex, England, to 
discuss mutual research interests. 

Drs. F. Andrew and R. Staples attended the annual 
meeting of the Teratology Society in Vancouver, Canada. 

Dr. F. de Serres met with Dr. Stitch in Vancouver, 
Canada, to discuss marine research. 



116 



August 1974 

Seven scientists from the NIEHS Pharmacology Branch 
presented papers at the Pharmacology Society Fall Meeting 
in Montreal, Canada. 

Dr. D. Hoel attended the Eighth International Biometric 
Conference in Constanta, Romania. 

Drs. R. Maurer, J. McLachlan, and R. Staples attended 
a meeting of the Society for the Study of Reproduction 
in Ottawa, Canada. 

NIEHS sponsored a trip by Drs. Roy Albert and Bernard 
Goldstein to Moscow, U.S.S.R., to participate in the U.S.- 
U.S.S.R. Environmental Health Agreement. 

September 1974 

Dr. W. Sheridan traveled to Stockholm, Sweden, and 
Munich, West Germany, for discussions with mutagenic 
researchers. 

Dr. L. Valcovic traveled to Munich and Uppsala, West 
Germany, to discuss current research programs and to 
present seminars. 

October 1974 

Drs. F. de Serres, W. Jurgelsky, and M. Lieberman 
attended the XI International Cancer Congress in Florence, 
Italy. 

Dr. E. Soares traveled to Toronto, Canada, for con- 
tinuation of collaborative research efforts with Dr. Bruce, 

Drs. Rail, Dixon, Gardner, Schambra, Staples, Drew, 
and Ms. Lange traveled to Moscow, U.S.S.R., to participate 
in the U.S.-U.S.S.R. Environmental Health Agreement. 

April 1975 

Dr. H. Mailing visited the Department of Genetics, 
University of Edinburgh, Scotland, and the Radiation and 
Environmental Hazard Research Laboratory, Munich, West 
Germany. 

Dr. H. Falk met with a group of experts concerned 
with marine pollution in London, England. 



117 



May 1975 

Drs. J. Fouts and J. Bend visited with Dr. Stitch in 
Vancouver, Canada, to discuss mutual research concerns. 

Drs. G. Hook and J. Crapo attended an international 
conference on lung diseases in Montreal, Canada. 

Dr. F. de Serres participated in the International 
Symposium on Genetic Hazards to Man from Environmental 
Agents in Ottawa, Canada. 

Dr. C. Langley presented a paper at the Symposium on 
Human Population Monitoring methods for Detecting In- 
creased Mutation Rates in Freiburg, West Germany, and 
visited laboratories in England and Denmark. 

Dr. J. Woods attended the First International Porphyrins 
Meeting in Freiburg, West Germany. 

Dr. D. McRee attended the International Microwave 
Power Symposium and the American National Standards In- 
stitute meeting in Waterloo, Canada. 

Drs. Lucier, McLachlan, and Schambra traveled to Moscow, 
U.S.S.R. to participate in the U.S.-U.S.S.R. Environmental 
Health Agreement 

June 1975 

Drs. D. Rail, F. de Serres, G. Lucier, and J. McLachlan 
attended the joint meeting of the European Society of 
Toxicology and the U.S. Society of Toxicology in Mont- 
pellier, France. Dr. de Serres also traveled to Brussels, 
Belgium, to attend a workshop on rapid screening tests to 
predict late toxic effects of environmental chemicals and 
to Paris, France, to participate in a conference "From 
Molecular Recognition to Perception." Drs. Lucier and 
McLachlan also visited research laboratories in Stockholm 
and Lund, Sweden. 

Dr. R. Drew attended an international conference 
"Radioactive Anomalies and Their Biological Implications," 
Pocos de Calda, Minas Gerais, Brazil. 

International Visitors to NIEHS 

Dr. G. Rentsch, Professor of Pharmacology, University 
of Heidelberg, and Research Director, Toxicology Research, 
Sandoz Ltd., Basle, Switzerland, was a guest of Drs. Hook 
and Fouts. While here, he discussed research with various 
branch scientists, gave an informal seminar, and demonstrated 
a technique for animal whole body perfusion (July 1974) . 



118 



Dr. Drew described aerotoxicology programs and showed 
the inhalation facilities to Dr. Komal , Undersecretary 
of State for Public Health, Thailand, and Dr. Sonchai , 
Director of the Thailand National Cancer Institute (August 
1974) . 

Dr. S. S. Parmer from India and currently visiting 
professor, Department of Physiology and Pharmacology, 
University of North Dakota, visited the Pharmacology 
Branch as a guest of Dr. Chhabra and discussed research 
with various branch scientists (September 1974) . 

Drs. Fouts and Drew met with Dr. C. Szymezykiewicy , 
Director of the Institute of Medicine in Mining and Metal- 
lurgical Industries, Zabrze, Poland, and discussed branch 
research and mutual interests in solvent toxicity and 
aerosol toxicology (September 1974) . 

Dr. Hart hosted a visit by Dr. Justyna Wisnieska-Knypl , 
Lodz, Poland. Dr. Wisnieska-Knypl discussed research 
programs, visited several branch laboratories, and learned 
liver perfusion techniques while here (November 1974) . 

Professor Christoffer Rappe , Department of Chemistry, 
University of Umea, Sweden, visited Dr. J. D. McKinney at 
NIEHS for research discussions on chlorinated hydrocarbon 
chemistry (November 1974) . 

Dr. Drew discussed animal and human exposures and vapor 
detectors with Dr. Lars Moelhave, Denmark (January 1975). 

Dr. Agthe of the International Agency for Research on 
Cancer, Lyon, France, met with Dr. Falk to discuss common 
interests and problems regarding the preparation of IARC 
monographs (January 19 75) . 

Dr. Preussmann, Heidelberg, Germany, visited NIEHS to 
discuss problems in assessment of carcinogenicity of 
chemicals with Dr. Falk (February 1975). 

Drs. U. A. Kuzminskaya and L. V. Marston of the All- 
Union Institute of Hygiene and Toxicology of Pesticides, 
Polymers and Plastics, of Kiev, U.S.S.R., discussed with 
Dr. Hart possible collaborative activities with Russian 
counterparts in pharmacokinetics; with Drs. Hart and Eling 
they discussed programs on PCB pharmacokinetics and lung 
accumulation of xenobiotics. Dr. Drew talked with them 
about the technology of inhalation exposures. Dr. Fouts 
discussed with them induction of mixed-function oxidases 
(MFOs) by pesticides and the best tests for induction in 
humans and provided them with bibliography and reprints of 
selected papers on human screening tests for MFO induction 
by pesticides (February-March 1975) . 



119 



Dr. Hart described branch research programs for Dr. R. 
Preussmann, Institute for Experimental Tumor Production 
and Tumor Treatment, Heidelberg, West Germany (February 
1975) . 

Dr. D. V. Parke, Department of Biochemistry, University 
of Surrey, Guildford, England, discussed with Dr. Fouts , 
U.S. -U.K. cooperative programs in environmental health 
sciences (March 1975) . 

Dr. Drew discussed aerotoxicology facilities and studies 
with Dr. E. Poulsen, Director, Institute of Toxicology, 
Denmark (March 1975) . 

Dr. Bernard Matter, Biological and Medical Research 
Division, Sandoz Ltd., Basle, Switzerland, met with members 
of the Microbial and Plant Genetics Section to discuss 
the micronuclei test systems for detecting mutagenicity 
of environmental agents (May 1975) . 



NATIONAL LIBRARY OF MEDICINE 



The National Library of Medicine (NLM) continued its 
international relationships which are based primarily on 
cooperative and sharing arrangements. The international 
character of the biomedical literature is illustrated 
by the fact that appoximately 64% of the 20,000 bio- 
medical periodicals acquired by NLM annually are non- 
U.S. From this massive amount of material, NLM has 
selected with the aid of consultants, 2,300 biomedical 
journals which form the corpus of our computerized 
activity, MEDLARS/MEDLINE, and our published Index 
Medicus . 

The Library has received many non-U. S. requests for 
the MEDLARS data base or for the services originating 
from it. Such requests were received even before the 
system became operational in 1964, and often from a 
number of institutions in the same country, all wishing 
to be designated as a MEDLARS center. 

A primary and continuing NLM decision throughout 
the years has been that any international arrangements 
relating to the MEDLARS system should be based on 
substantive technical cooperation. Today, the Library 
has eight bilateral arrangements with Australia, Canada, 
France, Germany, Japan, Sweden, the United Kingdom, and the 
World Health Organization. Table I shows their period 
of operation. These arrangements represent a sharing of 
time, talent, and resources with no transfer of funds. 
In return for access to the MEDLARS system, the partici- 
pating country agrees to provide: MEDLARS services to' 
its biomedical community; a document support service; 
indexed input to the NLM's MEDLARS system; and to pay 
for personnel sent to NLM for training in indexing and 
searching. 

The administrative setting for these MEDLARS centers 
varies from country . to country. The National Library 
of Medicine has maintained a policy of requiring the 
participating country to select the institution from 
among the many who have requested being a MEDLARS center. 
Thus, the MEDLARS center may be in an organization 
which is primarily concerned with medicine or health; a 
library; or an organization devoted broadly to science 
and technology. In each case, however, the center has 
been given a national mandate to serve the country. 
(Table II) 

It was envisaged that a unique role could be performed 
by the World Health Organization in providing service, 

121 



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124 



not only to its Technical Staff and Commissions, but to 
the developing countries that would receive information 
not available under other mechanisms of national 
auspices. WHO is in the early phases of this activity. 

The current NLM bilateral arrangements reflect 
MEDLARS II developments. A meeting of the International 
MEDLARS Policy Advisory Committee was held in November 
1975. This was the third such meeting of Policy Officials, 
accompanied by the Directors of the MEDLARS Centers. 
It reexamined the cooperative efforts, operational 
experience, regional coverage, networking, the availa- 
bility of TOXLINE/CHEMLINE and future collaboration. 

Exchange Programs 

Through the years the Library has developed coopera- 
tive exchanges and these now number 895 exchange partners 
in 85 countries throughout the world. This is a 
mechanism for acquiring material which may not be 
otherwise readily obtained. The program has been under 
review this year to ensure that there is an equivalence 
to the material being exchanged. 

The People's Republic of China is now an integral 
part of this exchange program and the Library receives 
five Chinese medical journals. This is in contrast 
to the 91 Chinese journals, including 30 major medical 
periodicals, which had been published and received 
prior to 1966. 

Aid Services 

The Library continues to provide services to 
developing countries under a special arrangement with 
the U.S. Agency for International Development. About 
20,000 such services are provided each year to 48 
developing countries throughout the world. The geographic 
distribution is estimated to be 29 percent to Latin 
America, 60.8 percent to the Near East, 8.3 percent to 
the Far East and 1.9 percent to Africa. This assistance 
responds to a demonstrated need in countries where there 
are insufficient medical literature resources. The 
services include interlibrary loans, reference requests, 
MEDLINE searches, loan of audiovisual materials, and 
subscriptions to Index Medicus and Abridged Index Medicus . 
Many aspects of medical research, education, public 
health and preventive medicine are encompassed in these 
services. The level of activity made possible by this 
NLM/AID agreement, however, does .iot respond totally to 
all needs of the developing nations. 



125 



Public Law 480 Programs 

About $10,000,000 equivalent in foreign currencies 
of seven countries has been obligated to date for the 
over-all program. At present, NLM sponsors projects 
in Poland, Israel, Yugoslavia, Tunisia, Egypt, India 
and Pakistan, including analytic critical reviews 
and biomedical monographs, histories of medicine, 
secondary literature tools in the health sciences (such 
as guides, atlases, handbooks), translations of current 
and historical foreign biomedical monographs and proceed- 
ings of international conferences. There is collaboration 
with major U.S. scientific societies, both to determine 
the need for studies in special biomedical areas, as well 
as to arrange for distribution in the United States. 
University presses and professional societies, as well 
as the National Technical Information Service, are 
utilized in the dissemination of studies funded under 
the Library's PL 480 program. 

During Fiscal Year 1975 the Library's Special 
Foreign Currency Program numbered 110 active projects 
in the seven participating countries, of which 10 were 
new projects. These were a monograph on the "Organization 
of Health Care" in Poland, a review of "Tuberculosis of 
the Spine" in India, a translation of a Russian monograph 
on "Brain and Activation," five critical reviews, and 
publication of two conference proceedings on enivronmental 
physiology and on diabetes and metabolite endocrinology. 
(Table III) About 70 percent of the program (primarily 
critical reviews) is prepared in Poland and Israel, with 
the remainder (largely translations) carried out in 
Tunisia, Egypt, India and Pakistan. During FY 1975 
sixteen publications resulting from PL 480 support were 
received. 

Foreign Visitors 

The Library receives more than 1,000 visitors 
annually from other countries - physicians, medical 
librarians and information specialists. In furthering 
the exchange of information and ideas, the Library 
arranges special programs for these visitors consistent 
with their professional responsibilities. Of concern to 
the many visitors to the Library were topics such as the 
concept of a national biomedical information resource; 
specialized information activities in cancer, cardio- 
vascular diseases and toxicology; health care and computer 
aided instruction. There were numerous study teams 
which included groups from Japan, Sweden, Pakistan, 
Germany, Algeria, U.S.S.R., Iran, Mexico, Trinidad and Tobago, 
and Egypt. 



126 

In Januaxy 1975 Dr. O.K. Harlem was appointed as a 
Visiting Scientist at the National Library of Medicine 
for one year. Dr. Harlem is a specialist in pediatrics, 
has been a general practitioner, a hospital physician, 
a university teacher and an editor. Dr. Harlem's 
contributions are in both the substance of medicine and 
in the communications and publication of biomedical 
information. He is developing a monograph during his 
stay at the National Library of Medicine which will form 
the basis of a course in biomedical communications 
within a medical school curriculum. 

National Biomedical Information Centers 

The National Library of Medicine, functioning as 
a national biomedical information resource, has attracted 
the interest of a number of governments who have expressed 
interest in establishing national biomedical information 
centers. The NLM does try to assist on a technical 
consultation basis. Although it does not provide foreign 
fellowships or have a formal training program, it is 
responsive to requests for the specialized training of 
physicians and information specialists who have been 
designated to direct a national information activity in 
their own country. 

Two specific arrangements have developed with 
Egypt and Iran. In October 1974 the Assistant Secretary 
for Health, HEW, and the Minister of Health of Egypt 
held a U.S. -Egyptian Joint Working Group meeting on Medical 
Cooperation. As a direct result of this meeting, the 
Chairman of the Board of Regents of NLM and the Library's 
Assistant Director for International Programs met with 
Egyptian officials to discuss potential collaboration in 
biomedical information. In July 1975 the second meeting 
of the full Joint Working Group met in Washington, D.C., 
at which time the Assistant Secretary, HEW, and the 
Minister of Health of Egypt agreed that both parties 
recognize that biomedical information is a necessary 
component of biomedical research, education and the 
delivery of health services. It was also agreed to explore 
cooperative arrangements which will result in improved 
biomedical communications between and within both countries. 
In particular, experiences will be shared which relate to 
the development of a national biomedical information resource 
and an operational national medical library system. 

At the request of the Minister of Science and Higher 
Education of Iran, the NLM has assisted in the planning 
of a national medical library and also in determining 
what bilateral cooperative relationships could be developed 
between the Imperial Medical Center of Iran and the U.S. 
National Library of Medicine. As a result, Iran is in the 
early stages of developing a national medical library and 



127 



information resource. On May 12 f 1975 the Director of the 
National Library of Medicine and the Minister of Science 
and Higher Education of Iran signed a Memorandum of 
Understanding under which NLM will provide technical 
consultation, training and specialized services as 
requested and funded by Iran. 

Regional Programs for Biomedical 
Information 

The regional approach taken by the Pan American 
Health Organization (PAHO) in its establishment of a 
Regional Library of Medicine (BIREME) in Sao Paulo, 
Brazil in 1967 has resulted in an effective operational 
activity. The NLM serves as a technical consultant 
and backstop to PAHO and BIREME. 

Since its first full year of operation in 1969, the 
collection of the Regional Library has been strengthened 
and the staff has increased both in number and in profes- 
sional expertise. BIREME has performed 218,000 loan 
services; prepared 5,255 special bibliographies; obtained 
and donated 266,000 journal issues to other Latin 
libraries and has provided specialized training to 263 
Latin health science librarians. 

As a result of the meeting of the Latin American 
Ministers in 1972, PAHO and BIREME have entered into 
agreements with Argentina, Peru, Chile, Colombia, Uruguay 
and Venezuela. Each of these countries is in the process 
of establishing a national center so that the transmittal 
of services can be channeled between BIREME and that focus. 
However, considerable effort is still needed to strengthen 
these national entities and crystallize their relationships 
into effective service linkages. 

The success of this PAHO undertaking has demonstrated 
that, even with political constraints and economic 
considerations, it is possible to cross boundaries with 
a regional/international effort devoted to the substance 
of biomedicine and the provision of information services. 
It is a recognition that improved biomedical communications 
will assist in the advancement of medical research, edu- 
cation and ultimately health care. 

The World Health Organization has been interested in 
developing such regional approaches in other areas of 
the world. To date, no formal step has yet been taken. 

International Organizations 

The National Library of Medicine has continued its 
membership in the International Council of Scientific 
Unions Abstracting Board (ICSU AB) and participates in 



128 

the deliberations of this organization. The organization 
is a meeting ground for information and abstracting organi- 
zations, private and governmental, from a number of coun- 
tries throughout the world, including the United Kingdom, 
France, Germany, Poland, Japan, South Africa, Canada, 
Belgium, The Netherlands and USSR. Important topics 
under consideration by ICSU AB are standardization, the 
economics of primary and secondary publications, the 
relationships between primary and secondary services and 
the information needs of developing countries. The 1976 
meeting of ICSU AB will, be hosted by the National 
Library of Medicine in Bethesda. 



NIH ASSISTANCE TO WHO AND PAHO 



During FY 1975 NIH continued to participate in acti- 
vities of the international organizations, particularly 
the World Health Organization (WHO) and the Pan American 
Health Organization (PAHO) . 

At the request of the Office of International 
Health (OIH) , NIH program areas assisted in the review 
of technical documents, working papers, and other program 
materials, and participated in the formulation of U.S. 
positions, many in connection with meetings of the 
governing bodies of the World Health Organization (World 
Health Assembly) , the Pan American Health Organization 
(Pan American Sanitary Conference) , and the International 
Agency for Research on Cancer (Governing Council) . 

NCI and FIC continued to participate with the OIH 
and the Department of State in defining the roles of 
international cancer agencies, including WHO, IARC, and 
the International Union against Cancer, and in defining 
WHO's role in the development and coordination of 
biomedical research. The NIH Director continued as a 
member of the PAHO Advisory Committee on Medical Research. 

NIH officials participated in formal meetings of 
international organizations, including service on U.S. 
delegations to meetings of their governing bodies. The 
Deputy Director, NCI, served as the U.S. representative 
to the 2-day annual meeting of the Governing Council of 
the International Agency for Research on Cancer (14th 
session, May 1975) and represented the United States at 
the WHO meeting of heads . of medical research councils 
(December 1974) . 

The National Library of Medicine continued to col- 
laborate with activities of the PAHO Regional Library of 
Medicine, established at the Federal University of Sao 
Paulo, Brazil, which provides services in the health 
sciences to all of South America. The NLM Director 
participated in the Seventh Meeting of the Scientific 
Advisory Committee. 

The Director, Center for Population Research, NICHD, 
continued to serve on the Advisory Group to the WHO 
Expanded Program of Research, Development, and Research 
Training in Human Reproduction. This WHO program focuses 
on the urgent need to develop a variety of safe, effective 
and acceptable methods for the regulation of human fertility, 

During FY 197 5, six NIH laboratories continued to 
serve as Regional or International Collaborating Centers 



129 



130 



for the World Health Organization; Collaborating Center 
for Immunology, NCI; Collaborating Center for Malaria, 
NIAID; Collaborating Center for Respiratory Viruses Other 
Than Influenza, NIAID; Collaborating Center for Human 
Rickettsioses, NIAID; Collaborating Center for Comparative 
Medicine, NCI; and Collaborating Center for Mycoplasmas, 
NIAID. In May 1974 the Division of Research Services, 
NIH, was designated as the WHO Collaborating Center for 
Defined Laboratory Animals. 

Several NIH programs contracted to support specific 
activities of PAHO, WHO, and IARC. NIAID, for example, 
supported the First Inter-American Conference on Conserva- 
tion and Utilization of American Nonhuman Primates in 
Biomedical Research, held in Lima, Peru, June 2-4, 1975. 

Some 50 NIH scientists served as advisors or consult- 
ants to WHO/PAHO. Two NIH employees were on long-term 
detail to WHO and one each to PAHO and IARC. An NLM 
official, transferred to WHO, continued to serve as chief 
of WHO's Library services. During the fiscal year many 
NIH staff members continued to serve as members of a 
variety of WHO expert advisory panels and participated 
in their committee meetings. 

Two programs (NIEHS and NIAID) were provided consult- 
ant services by WHO. (This WHO activity provides "techni- 
cal assistance" to U.S. domestic programs.) 



131 



UNITED STATES FELLOWS AND TRAINEES 
ABROAD 



The sponsoring of U.S. Fellows and Trainees for Re- 
search and Training Abroad began with the establishment 
of the several insitutes at NIH. The criteria originally 
developed to select training locations for fellows and 
trainees provided that they might attend any qualified 
institution in the United States; study abroad was 
authorized only when satisfactory evidence was provided 
that the type or quality of training abroad was parti- 
cularly suited for their purpose and could best be 
obtained there. This program, which is administered 
by the individual institutes, began with one fellowship 
award made in 1947. The peak year for U.S. fellows and 
trainees abroad was FY 1966 with 397 awards. Since FY 
1966 foreign training has been reduced due to budgetary 
controls. 



GUEST WORKERS 



Under the Guest Worker Program, the NIH may invite 
individuals, other than employees or fellows of the NIH, 
who are sponsored by qualified organizations to utilize 
the research facilities of the NIH for the purpose of 
carrying on a research project or participating in a 
research program. The basis for acceptance of a guest 
worker rests on complementary professional interest, 
appropriate facilities, and the prospect of mutual 
benefit to the host bureau, institute or division and 
the guest worker. During FY 1975, 184 scientists from 
42 countries worked at the NIH under this program. 



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